ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.3408+5G>A

gnomAD frequency: 0.00001  dbSNP: rs760279912
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Total submissions: 2
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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 RCV001195510 SCV001365888 uncertain significance not specified 2019-03-15 criteria provided, single submitter clinical testing The c.3408+5G>Avariant in OTOF has not been previously reported in individuals with hearing loss or auditory neuropathy spectrum disorder, but has been identified in 0.0017% (2/112866) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational splice prediction tools suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3.
Invitae RCV002560202 SCV003499789 uncertain significance not provided 2022-05-18 criteria provided, single submitter clinical testing This sequence change falls in intron 27 of the OTOF gene. It does not directly change the encoded amino acid sequence of the OTOF protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs760279912, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with OTOF-related conditions. ClinVar contains an entry for this variant (Variation ID: 930086). 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 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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