ClinVar Miner

Submissions for variant NM_000345.4(SNCA):c.88G>C (p.Ala30Pro)

dbSNP: rs104893878
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics, Royal Melbourne Hospital RCV000015045 SCV002503806 likely pathogenic Autosomal dominant Parkinson disease 1 2020-11-20 criteria provided, single submitter clinical testing This sequence change is predicted to replace alanine with proline at codon 30 of the SNCA protein (p.(Ala30Pro)). The alanine residue is evolutionarily conserved (100 vertebrates, UCSC), and is located in an N-terminal domain helix. There is a small physicochemical difference between alanine and glycine. The variant is absent in a large population cohort (PM2; gnomAD v2.1 and v3.0). It has been shown to co-segregate with Parkinson disease in a single family (PP1; PMID: 11376188). Additionally, mouse models of the variant recapitulate the human Parkinson disease phenotype and brain pathology (PS3; PMID: 21559878, 31267130). Multiple lines of computational evidence predict a deleterious effect for the missense substitution (PP3; 6/6 algorithms). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as a LIKELY PATHOGENIC . Following criteria are met: PS3, PM2, PP1, PP3.
OMIM RCV000015045 SCV000035301 pathogenic Autosomal dominant Parkinson disease 1 2013-11-22 no assertion criteria provided literature only

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