ClinVar Miner

Submissions for variant NM_000441.2(SLC26A4):c.765+5G>A

gnomAD frequency: 0.00001  dbSNP: rs947864801
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001569897 SCV001794064 uncertain significance not provided 2023-03-29 criteria provided, single submitter clinical testing Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
Institute of Rare Diseases, West China Hospital, Sichuan University RCV005052836 SCV005687383 likely pathogenic Autosomal recessive nonsyndromic hearing loss 4 2025-01-09 criteria provided, single submitter research PP3;PM3_Strong;PP4;PM2_Supporting
Labcorp Genetics (formerly Invitae), Labcorp RCV001569897 SCV005707466 likely pathogenic not provided 2024-05-29 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 present in population databases (no rsID available, gnomAD 0.01%). This variant has been observed in individual(s) with clinical features of SLC26A4-related conditions (Invitae). 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: 1203752). 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. 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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