ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.765+3A>C

dbSNP: rs483353048
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory; Baylor College of Medicine RCV000119812 SCV000154738 probable-pathogenic Autosomal recessive nonsyndromic hearing loss 4 criteria provided, single submitter not provided Converted during submission to Likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854588 SCV002280960 likely pathogenic not provided 2023-10-22 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the SLC26A4 gene. It does not directly change the encoded amino acid sequence of the SLC26A4 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with deafness (PMID: 25991456). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 133301). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.765+3A nucleotide in the SLC26A4 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 23336812, 31033086). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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