ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.1065+5C>T (rs201597816)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000616560 SCV000722534 likely benign not specified 2017-09-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000804989 SCV000944930 uncertain significance Propionic acidemia 2018-12-04 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the PCCA gene. It does not directly change the encoded amino acid sequence of the PCCA protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs201597816, ExAC 0.2%). This variant has not been reported in the literature in individuals with PCCA-related disease. ClinVar contains an entry for this variant (Variation ID: 511808). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.
Illumina Clinical Services Laboratory,Illumina RCV000804989 SCV001266744 uncertain significance Propionic acidemia 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001529879 SCV001744114 likely benign not provided no assertion criteria provided clinical testing

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