ClinVar Miner

Submissions for variant NM_001330691.3(CEP78):c.491G>A (p.Gly164Asp)

gnomAD frequency: 0.00012  dbSNP: rs200752089
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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 RCV000825893 SCV000967378 uncertain significance not specified 2018-09-13 criteria provided, single submitter clinical testing The p.Gly164Asp variant in CEP78 has not been previously reported in individuals with hearing loss or cone-rod dystrophy, but has been identified in 0.03% (27/9 4664) European chromosomes by the Genome Aggregation Database (gnomAD, http://gn omad.broadinstitute.org). Computational prediction tools and conservation analys is suggest that the p.Gly164Asp variant may impact the protein, though this info rmation is not predictive enough to determine pathogenicity. In summary, the cli nical significance of the p.Gly164Asp variant is uncertain. ACMG/AMP Criteria ap plied: PP3, PM2_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001047659 SCV001211630 likely pathogenic not provided 2024-11-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 164 of the CEP78 protein (p.Gly164Asp). This variant is present in population databases (rs200752089, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of CEP78-related conditions (internal data). 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: 667216). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CEP78 protein function with a positive predictive value of 80%. 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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