ClinVar Miner

Submissions for variant NM_021954.4(GJA3):c.427G>A (p.Gly143Arg)

dbSNP: rs398122937
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Dept. Genetics and Cancer, Menzies Institute for Medical Research, University of Tasmania RCV000043651 SCV005081802 likely pathogenic Cataract 14 multiple types 2023-01-21 criteria provided, single submitter curation Variant identified and curated during a GJA3 specific review of the literature in relation to pediatric or congenital cataract. ACMG-AMP criteria applied: PP1(Strong), PS4(Supporting), PM2(Supporting), PP3. Original variant report: PMID:22876138;34169787. The cataract phenotype reported for this variant is: Pulverulent disk-like (Coppock). Gene review and curation guidelines are outlined in: https://doi.org/10.1080/17469899.2023.2160320
Labcorp Genetics (formerly Invitae), Labcorp RCV000043651 SCV005835540 pathogenic Cataract 14 multiple types 2024-05-09 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 143 of the GJA3 protein (p.Gly143Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant congenital cataract (PMID: 22876138). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 50945). 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 GJA3 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects GJA3 function (PMID: 24019978). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000043651 SCV000071673 pathogenic Cataract 14 multiple types 2012-01-01 no assertion criteria provided literature only

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