{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:14:24Z","timestamp":1787861664291,"version":"build-2784847793"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2015\/19\/B\/NZ2\/01824"],"award-info":[{"award-number":["2015\/19\/B\/NZ2\/01824"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Actin molecules are fundamental for embryonic structural and functional differentiation; \u03b3-actin is specifically required for the maintenance and function of cytoskeletal structures in the ear, resulting in hearing. Baraitser\u2013Winter Syndrome (B-WS, OMIM #243310, #614583) is a rare, multiple-anomaly genetic disorder caused by mutations in either cytoplasmically expressed actin gene, ACTB (\u03b2-actin) or ACTG1 (\u03b3-actin). The resulting actinopathies cause characteristic cerebrofrontofacial and developmental traits, including progressive sensorineural deafness. Both ACTG1-related non-syndromic A20\/A26 deafness and B-WS diagnoses are characterized by hypervariable penetrance in phenotype. Here, we identify a 28th patient worldwide carrying a mutated \u03b3-actin ACTG1 allele, with mildly manifested cerebrofrontofacial B-WS traits, hypervariable penetrance of developmental traits and sensorineural hearing loss. This patient also displays brachycephaly and a complete absence of speech faculty, previously unreported for ACTG1-related B-WS or DFNA20\/26 deafness, representing phenotypic expansion. The patient\u2019s exome sequence analyses (ES) confirms a de novo ACTG1 variant previously unlinked to the pathology. Additional microarray analysis uncover no further mutational basis for dual molecular diagnosis in our patient. We conclude that \u03b3-actin c.542C &gt; T, p.Ala181Val is a dominant pathogenic variant, associated with mildly manifested facial and cerebral traits typical of B-WS, hypervariable penetrance of developmental traits and sensorineural deafness. We further posit and present argument and evidence suggesting ACTG1-related non-syndromic DFNA20\/A26 deafness is a manifestation of undiagnosed ACTG1-related B-WS.<\/jats:p>","DOI":"10.3390\/ijms23020692","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T20:29:26Z","timestamp":1641760166000},"page":"692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["De Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser\u2013Winter Syndrome"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-8722","authenticated-orcid":false,"given":"Mateusz","family":"Dawidziuk","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5295-7363","authenticated-orcid":false,"given":"Anna","family":"Kutkowska-Kazmierczak","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-1696","authenticated-orcid":false,"given":"Ewelina","family":"Bukowska-Olech","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Jurek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Kalka","sequence":"additional","affiliation":[{"name":"Unit of Anthropology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy Lys","family":"Guilbride","sequence":"additional","affiliation":[{"name":"Independent Researcher, Manhi\u00e7a MPT 1122, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz Ireneusz","family":"Furmanek","sequence":"additional","affiliation":[{"name":"Department of Radiology and Diagnostic Imaging, Centre for Postgraduate Medical Education, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1787-3425","authenticated-orcid":false,"given":"Monika","family":"Bekiesinska-Figatowska","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Bal","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-5834","authenticated-orcid":false,"given":"Pawel","family":"Gawlinski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1146\/annurev.bi.55.070186.005011","article-title":"Actin and actin-binding proteins. A critical evaluation of mechanisms and functions","volume":"55","author":"Pollard","year":"1986","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","first-page":"1775","article-title":"Structure, chromosome location, and expression of the human gamma-actin gene: Differential evolution, location, and expression of the cytoskeletal beta- and gamma-actin genes","volume":"8","author":"Erba","year":"1988","journal-title":"Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1242\/jcs.110.6.765","article-title":"Sorting of actin isoforms in chicken auditory hair cells","volume":"110","author":"Ness","year":"1997","journal-title":"J. Cell Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/341397a0","article-title":"How the ear\u2019s works work","volume":"341","author":"Hudspeth","year":"1989","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1146\/annurev.biophys.29.1.545","article-title":"Molecular mechanisms controlling actin filament dynamics in nonmuscle cells","volume":"29","author":"Pollard","year":"2000","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1083\/jcb.96.3.822","article-title":"Actin filaments, stereocilia, and hair cells of the bird cochlea. II. Packing of actin filaments in the stereocilia and in the cuticular plate and what happens to the organization when the stereocilia are bent","volume":"96","author":"Tilney","year":"1983","journal-title":"J. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1083\/jcb.95.1.249","article-title":"Interactions between actin filaments and between actin filaments and membranes in quick-frozen and deeply etched hair cells of the chick ear","volume":"95","author":"Hirokawa","year":"1982","journal-title":"J. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/ejhg.2014.95","article-title":"Baraitser-Winter cerebrofrontofacial syndrome: Delineation of the spectrum in 42 cases","volume":"23","author":"Verloes","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.1002\/ajmg.a.37771","article-title":"Update on the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome","volume":"170","author":"Kuechler","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3109\/13816810.2016.1164196","article-title":"A novel mutation in ACTG1 causing Baraitser-Winter syndrome with extremely variable expressivity in three generations","volume":"38","author":"Kemerley","year":"2017","journal-title":"Ophthalmic Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.seizure.2020.05.023","article-title":"Targeted re-sequencing in malformations of cortical development: Genotype-phenotype correlations","volume":"80","author":"Accogli","year":"2020","journal-title":"Seizure"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s11427-017-9165-2","article-title":"A novel de novo mutation of ACTG1 in two sporadic non-syndromic hearing loss cases","volume":"61","author":"Wang","year":"2018","journal-title":"Sci. China Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7056","DOI":"10.1038\/s41598-020-63690-5","article-title":"Novel, ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss","volume":"10","author":"Miyajima","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1056\/NEJMoa1516767","article-title":"Resolution of disease phenotypes resulting from multilocus genomic variation","volume":"376","author":"Posey","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"84S","DOI":"10.1177\/0003489415575057","article-title":"Mutational spectrum and clinical features of patients with ACTG1 mutations identified by massively parallel DNA sequencing","volume":"124","author":"Miyagawa","year":"2015","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1177\/000348940911800511","article-title":"Audiometric and vestibular features in a second Dutch, DFNA20\/26 family with a novel mutation in ACTG1","volume":"118","author":"Huygen","year":"2009","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103877","DOI":"10.1016\/j.ejmg.2020.103877","article-title":"Previously undescribed phenotypic findings and novel ACTG1 gene pathogenic variants in Baraitser-Winter cerebrofrontofacial syndrome","volume":"63","author":"Villarroel","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3389\/fgene.2018.00681","article-title":"Genomic studies in a large cohort of hearing impaired haract patients revealed several new alleles, a rare case of uniparental disomy (UPD) and the importance to search for copy number variations","volume":"9","author":"Morgan","year":"2018","journal-title":"Front Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/humu.23246","article-title":"A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma","volume":"38","author":"Rainger","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gieldon, L., Mackenroth, L., Kahlert, A.K., Lemke, J.R., Porrmann, J., Schallner, J., von der Hagen, M., Markus, S., Weidensee, S., and Novotna, B. (2018). Diagnostic value of partial exome sequencing in developmental disorders. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201041"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ejmg.2015.06.006","article-title":"Rare, ACTG1 variants in fetal microlissencephaly","volume":"58","author":"Poirier","year":"2015","journal-title":"Eur. J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00439-016-1648-8","article-title":"Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss","volume":"135","author":"Bierer","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1086\/379286","article-title":"Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20\/26)","volume":"73","author":"Zhu","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1093\/hmg\/ddp249","article-title":"In vivo and in vitro effects of two novel gamma-actin (ACTG1) mutations that cause DFNA20\/26 hearing impairment","volume":"18","author":"Bryan","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/ng.1091","article-title":"De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome","volume":"44","author":"Hoischen","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S1673-8527(08)60075-2","article-title":"Novel, ACTG1 mutation causing autosomal dominant non-syndromic hearing impairment in a Chinese family","volume":"35","author":"Liu","year":"2008","journal-title":"J. Genet. Genom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/j.ajhg.2019.11.003","article-title":"Sex-based analysis of de novo variants in neurodevelopmental disorders","volume":"105","author":"Turner","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cabanillas, R., Di\u00f1eiro, M., Cifuentes, G.A., Castillo, D., Pruneda, P.C., \u00c1lvarez, R., S\u00e1nchez-Dur\u00e1n, N., Cap\u00edn, R., Plasencia, A., and Viejo-D\u00edaz, M. (2018). Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients. BMC Med. Genom., 11.","DOI":"10.1186\/s12920-018-0375-5"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16783","DOI":"10.1038\/s41598-017-16846-9","article-title":"Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients","volume":"7","author":"Baux","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13073-021-00855-5","article-title":"Integration of whole genome sequencing into a healthcare setting: High diagnostic rates across multiple clinical entities in 3219 rare disease patients","volume":"13","author":"Stranneheim","year":"2021","journal-title":"Genome Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Miyagawa, M., Naito, T., Nishio, S.Y., Kamatani, N., and Usami, S. (2013). Targeted exon sequencing successfully discovers rare causative genes and clarifies the molecular epidemiology of Japanese deafness patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071381"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00439-017-1774-y","article-title":"Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia","volume":"136","author":"Longoni","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1750-1172-7-60","article-title":"Targeted massive parallel sequencing: The effective detection of novel causative mutations associated with hearing loss in small families","volume":"7","author":"Baek","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/gim.2015.148","article-title":"Clinical application of whole-exome sequencing across clinical indications","volume":"18","author":"Retterer","year":"2016","journal-title":"Genet. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3389\/fphys.2019.00623","article-title":"Post-mortem characterization of a case with an ACTG1 variant, agenesis of the corpus callosum and neuronal heterotopia","volume":"10","author":"Vontell","year":"2019","journal-title":"Front Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"fcaa221","DOI":"10.1093\/braincomms\/fcaa221","article-title":"Genetic heterogeneity of polymicrogyria: Study of 123 patients using deep sequencing","volume":"3","author":"Stutterd","year":"2020","journal-title":"Brain Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41436-018-0075-8","article-title":"Clinical genome sequencing in an unbiased pediatric cohort","volume":"21","author":"Thiffault","year":"2019","journal-title":"Genet. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.braindev.2019.05.007","article-title":"Genomic backgrounds of Japanese patients with undiagnosed neurodevelopmental disorders","volume":"41","author":"Yamamoto","year":"2019","journal-title":"Brain Dev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yuan, Y., Gao, X., Huang, B., Lu, J., Wang, G., Lin, X., Qu, Y., and Dai, P. (2016). Phenotypic heterogeneity in a DFNA20\/26 family segregating a novel ACTG1 mutation. BMC Genet., 17.","DOI":"10.1186\/s12863-016-0333-1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jpeds.2019.08.024","article-title":"Genetic disorders in prenatal onset syndromic short stature identified by exome sequencing","volume":"215","author":"Homma","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/ng.3970","article-title":"Contribution of rare inherited and de novo variants in 2, 871 congenital heart disease probands","volume":"49","author":"Jin","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ejhg.2016.182","article-title":"The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands","volume":"25","author":"Wesdorp","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/1750-1172-8-172","article-title":"Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: A cross-sectional, multi-center next-generation sequencing study","volume":"8","author":"Mutai","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1136\/jmg.40.12.879","article-title":"A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20\/26)","volume":"40","author":"Krieger","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Miyagawa, M., Nishio, S.Y., Ikeda, T., Fukushima, K., and Usami, S. (2013). Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075793"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Park, G., Gim, J., Kim, A.R., Han, K.H., Kim, H.S., Oh, S.H., Park, T., Park, W.Y., and Choi, B.Y. (2013). Multiphasic analysis of whole exome sequencing data identifies a novel mutation of ACTG1 in a nonsyndromic hearing loss family. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-191"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1186\/s12967-014-0311-1","article-title":"Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss","volume":"12","author":"Wei","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/gim.2014.65","article-title":"Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations","volume":"16","author":"Vona","year":"2014","journal-title":"Genet. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/jhg.2015.143","article-title":"An effective screening strategy for deafness in combination with a next-generation sequencing platform: A consecutive analysis","volume":"61","author":"Sakuma","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/sj.ejhg.5201670","article-title":"A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian, DFNA20\/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment","volume":"14","author":"Rendtorff","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/humu.22999","article-title":"DNA diagnostics of hereditary hearing loss: A targeted resequencing approach combined with a mutation classification system","volume":"37","author":"Sommen","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41525-019-0098-3","article-title":"A large data resource of genomic copy number variation across neurodevelopmental disorders","volume":"4","author":"Zarrei","year":"2019","journal-title":"NPJ Genom. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"582","DOI":"10.3390\/audiolres11040052","article-title":"DFNA20\/26 and other ACTG1-associated phenotypes: A case report and review of the literature","volume":"11","author":"Sorrentino","year":"2021","journal-title":"Audiol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"543528","DOI":"10.3389\/fgene.2020.543528","article-title":"Genomic analysis of korean patient with microcephaly","volume":"11","author":"Lee","year":"2021","journal-title":"Front. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13073-020-00803-9","article-title":"dbNSFP v4, a comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs","volume":"12","author":"Liu","year":"2020","journal-title":"Genome Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:27:05Z","timestamp":1760362025000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,8]]},"references-count":56,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23020692"],"URL":"https:\/\/doi.org\/10.3390\/ijms23020692","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,8]]}}}