ClinVar Miner

Submissions for variant NM_001298.3(CNGA3):c.485A>T (p.Asp162Val)

gnomAD frequency: 0.00010  dbSNP: rs747447519
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001956242 SCV002240056 pathogenic not provided 2023-10-31 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 162 of the CNGA3 protein (p.Asp162Val). This variant is present in population databases (rs747447519, gnomAD 0.07%). This missense change has been observed in individuals with achromatopsia and/or cone dysfunction syndrome (PMID: 11536077, 24148654, 28341476). ClinVar contains an entry for this variant (Variation ID: 1458185). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CNGA3 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CNGA3 function (PMID: 17693388). For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV003388620 SCV004100366 uncertain significance Achromatopsia 2 criteria provided, single submitter clinical testing The missense variant p.D162V in CNGA3 (NM_001298.3) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. There is a large physicochemical difference between aspartic acid and valine, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. The p.D162V missense variant is predicted to be damaging by both SIFT and PolyPhen2. The aspartic acid residue at codon 162 of CNGA3 is conserved in all mammalian species. The nucleotide c.485 in CNGA3 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003388620 SCV004807037 likely pathogenic Achromatopsia 2 2024-03-26 criteria provided, single submitter clinical testing

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