ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.1746G>A (p.Ser582=) (rs192171304)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672493 SCV000797600 uncertain significance Propionic acidemia 2018-01-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000672493 SCV001362339 pathogenic Propionic acidemia 2019-01-21 criteria provided, single submitter clinical testing Variant summary: PCCA c.1746G>A (p.Ser582Ser) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes a 5' splicing donor site. Four predict the variant weakens a 5' donor site. These predictions are supported by a functional study that reported an impact on mRNA splicing (Yang_2004). The variant allele was found at a frequency of 1.6e-05 in 245876 control chromosomes . c.1746G>A has been reported in the literature in a homozygote and compound heterozygote individuals affected with Propionic Acidemia (Yang_2004, Kraus_2012). The homozygote individual was found to have less than 10% PCC activity (Kraus_2012). These data indicate that the variant may be associated with disease. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic.

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