ClinVar Miner

Submissions for variant NM_000287.4(PEX6):c.295C>T (p.Arg99Trp)

gnomAD frequency: 0.00003  dbSNP: rs772383329
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000341285 SCV000463362 uncertain significance Peroxisome biogenesis disorder 4A (Zellweger) 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.
Counsyl RCV000667442 SCV000791886 uncertain significance Peroxisome biogenesis disorder 4A (Zellweger); Peroxisome biogenesis disorder 4B 2017-05-30 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075627 SCV001241254 uncertain significance Retinal dystrophy 2019-02-08 criteria provided, single submitter clinical testing
Invitae RCV001850902 SCV002181489 uncertain significance Peroxisome biogenesis disorder 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 99 of the PEX6 protein (p.Arg99Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PEX6-related conditions. ClinVar contains an entry for this variant (Variation ID: 356806). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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