ClinVar Miner

Submissions for variant NM_003801.4(GPAA1):c.149T>A (p.Met50Lys)

gnomAD frequency: 0.00004  dbSNP: rs200581623
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001546731 SCV001766303 pathogenic not provided 2022-10-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34703884)
Institute of Human Genetics, University of Leipzig Medical Center RCV001780406 SCV002026403 uncertain significance Glycosylphosphatidylinositol biosynthesis defect 15 2021-10-11 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous with NM_003801.4:c.1477_1478del._x000D_ Criteria applied: PM3, PS4_SUP, PM2_SUP, PP3
Invitae RCV001546731 SCV002222616 uncertain significance not provided 2023-09-25 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 50 of the GPAA1 protein (p.Met50Lys). This variant is present in population databases (rs200581623, gnomAD 0.005%). This missense change has been observed in individual(s) with congenital disorder of glycosylation (GPAA1-CDG) (PMID: 34703884). 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: 1187326). 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 GPAA1 protein function. 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.
CeGaT Center for Human Genetics Tuebingen RCV001546731 SCV002564027 likely pathogenic not provided 2023-11-01 criteria provided, single submitter clinical testing GPAA1: PM3:Strong, PM2

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