ClinVar Miner

Submissions for variant NM_001739.2(CA5A):c.697T>C (p.Ser233Pro)

gnomAD frequency: 0.00001  dbSNP: rs587777316
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000114946 SCV003272612 uncertain significance Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency 2022-09-26 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 233 of the CA5A protein (p.Ser233Pro). This variant is present in population databases (rs587777316, gnomAD 0.005%). This missense change has been observed in individual(s) with carbonic anhydrase VA deficiency (PMID: 24530203). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 127087). 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 CA5A protein function. Experimental studies have shown that this missense change affects CA5A function (PMID: 24530203, 26913920). 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.
GeneDx RCV003126499 SCV003803277 likely pathogenic not provided 2022-08-11 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect of p.(S233P) on enzymatic activity of carbonic anhydrase VA (van Karnebeek et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26913920, 24530203)
OMIM RCV000114946 SCV000148850 pathogenic Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency 2014-03-06 no assertion criteria provided literature only
GeneReviews RCV000114946 SCV000221286 not provided Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency no assertion provided literature only

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