Submissions for variant NM_194248.3(OTOF):c.4228-1G>T

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003490900	SCV004241513	likely pathogenic	Nonsyndromic genetic hearing loss	2023-12-14	criteria provided, single submitter	clinical testing	Variant summary: OTOF c.4228-1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251458 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4228-1G>T in individuals affected with Nonsyndromic Hearing Loss And Deafness, Type 9 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.