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Many SAVs have been predicted to strongly affect molecular protein function. Common SAVs (&gt;\u20095% of population) were predicted to have, on average, more effect on molecular protein function than rare SAVs (&lt;\u20091% of population). We hypothesized that the prevalence of effect in common over rare SAVs might partially be caused by common SAVs more often occurring at interfaces of proteins with other proteins, DNA, or RNA, thereby creating subgroup-specific phenotypes. We analyzed SAVs from 60,706 people through the lens of two prediction methods, one (SNAP2) predicting the effects of SAVs on molecular protein function, the other (ProNA2020) predicting residues in DNA-, RNA- and protein-binding interfaces.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Three results stood out. Firstly, SAVs predicted to occur at binding interfaces were predicted to more likely affect molecular function than those predicted as not binding (<jats:italic>p<\/jats:italic> value\u2009&lt;\u20092.2\u2009\u00d7\u200910<jats:sup>\u201316<\/jats:sup>). Secondly, for SAVs predicted to occur at binding interfaces, common SAVs were predicted more strongly with effect on protein function than rare SAVs (<jats:italic>p<\/jats:italic> value\u2009&lt;\u20092.2\u2009\u00d7\u200910<jats:sup>\u201316<\/jats:sup>). Restriction to SAVs with experimental annotations confirmed all results, although the resulting subsets were too small to establish statistical significance for any result. Thirdly, the fraction of SAVs predicted at binding interfaces differed significantly between tissues, e.g. urinary bladder tissue was found abundant in SAVs predicted at protein-binding interfaces, and reproductive tissues (ovary, testis, vagina, seminal vesicle and endometrium) in SAVs predicted at DNA-binding interfaces.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Overall, the results suggested that residues at protein-, DNA-, and RNA-binding interfaces contributed toward predicting that common SAVs more likely affect molecular function than rare SAVs.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-020-03759-0","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T14:02:55Z","timestamp":1602597775000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Protein\u2013protein and protein-nucleic acid binding residues important for common and rare sequence variants in human"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1790-8536","authenticated-orcid":false,"given":"Jiajun","family":"Qiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitrii","family":"Nechaev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkhard","family":"Rost","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,13]]},"reference":[{"issue":"1","key":"3759_CR1","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1038\/s41598-017-01054-2","volume":"7","author":"Y Mahlich","year":"2017","unstructured":"Mahlich Y, Reeb J, Hecht M, Schelling M, De Beer TAP, Bromberg Y, Rost B. 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