ClinVar Miner

Submissions for variant NM_016239.4(MYO15A):c.5964+3G>C

gnomAD frequency: 0.00009  dbSNP: rs530975087
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156056 SCV000205769 uncertain significance not specified 2013-10-11 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The 5964+3G>C varia nt in MYO15A has not been reported in individuals with hearing loss, and frequen cy data from large population studies is insufficient. This variant is located in the 5' splice region but not in the invariant +1/+2 positions in the splice s ite consensus sequence. Computational tools do not suggest and impact to splicin g; however, this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty; however based upon splice site computational data, we would lean tow ards a more likely benign role.
Molecular Diagnosis Center for Deafness RCV001254924 SCV001332616 pathogenic Autosomal recessive nonsyndromic hearing loss 3 2020-02-27 criteria provided, single submitter case-control
GeneDx RCV001570481 SCV001794780 uncertain significance not provided 2021-04-05 criteria provided, single submitter clinical testing In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Labcorp Genetics (formerly Invitae), Labcorp RCV001570481 SCV002108829 uncertain significance not provided 2022-02-05 criteria provided, single submitter clinical testing This sequence change falls in intron 26 of the MYO15A gene. It does not directly change the encoded amino acid sequence of the MYO15A protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs530975087, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MYO15A-related conditions. ClinVar contains an entry for this variant (Variation ID: 179269). 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.5964+3G nucleotide in the MYO15A gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 24206587, 30953472). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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