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A comprehensive evaluation of reported studies on hereditary male infertility revealed that the 2,404 pathogenic variants contained 120 canonical splicing variants and 32 NCSVs. Among the remaining 2,252 variants, the splicing variant analytical strategy identified 17 novel NCSVs that disrupt normal mRNA splicing from previously classified missense variants. This expands the contribution of NCSVs by 53.13% (17\/32), with NCSVs accounting for 28.99% (49\/169) of all the splicing variants. Moreover, thirteen positively validated NCSVs are identified in 12 of 718 idiopathic male infertility patients with negative results by conventional genetic analysis. The first pathogenic variant in the TATA element modulatory factor 1 (\n                    <jats:italic>TMF1<\/jats:italic>\n                    : c.2859+4A&gt;G) results in\n                    <jats:italic>TMF1<\/jats:italic>\n                    exon 14 skipping and decreased progressive sperm motility and morphological abnormalities in a patient with male infertility.\n                    <jats:italic>Tmf1<\/jats:italic>\n                    NCSV knock\u2010in mice recapitulated human phenotype, showing significantly decreased sperm count, motility, ultrastructural head defects, and subfertility. This study provides the first comprehensive landscape of NCSVs in male infertility, suggesting that NCSVs may constitute a hidden etiological factor for male infertility.\n                  <\/jats:p>","DOI":"10.1002\/advs.202515512","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:09:14Z","timestamp":1761894554000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping the Non\u2010Canonical Splicing Variants: Decrypting the Hidden Genetic Architecture of Idiopathic Male Infertility"],"prefix":"10.1002","volume":"13","author":[{"given":"Kuokuo","family":"Li","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center Department of Obstetrics and Gynecology The First Affiliated Hospital of Anhui Medical University  No. 218 Jixi Road Hefei Anhui 230022 China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical 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