ClinVar Miner

Submissions for variant NM_002617.4(PEX10):c.977G>A (p.Arg326His)

gnomAD frequency: 0.00001  dbSNP: rs140890506
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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 RCV000286286 SCV000355600 uncertain significance Peroxisome biogenesis disorder 6A (Zellweger) 2018-01-13 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 RCV000667284 SCV000791710 uncertain significance Peroxisome biogenesis disorder 6A (Zellweger); Peroxisome biogenesis disorder 6B 2017-05-26 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000667284 SCV000894767 uncertain significance Peroxisome biogenesis disorder 6A (Zellweger); Peroxisome biogenesis disorder 6B 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV002520464 SCV003447312 uncertain significance Peroxisome biogenesis disorder, complementation group 7 2022-08-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 346 of the PEX10 protein (p.Arg346His). 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 PEX10-related conditions. ClinVar contains an entry for this variant (Variation ID: 296272). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.

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