ClinVar Miner

Submissions for variant NM_000288.4(PEX7):c.120C>G (p.Tyr40Ter) (rs61753238)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763558 SCV000894378 pathogenic Phytanic acid storage disease; Rhizomelic chondrodysplasia punctata type 1; Peroxisome biogenesis disorder 9B 2018-10-31 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000147254 SCV000194624 pathogenic Rhizomelic chondrodysplasia punctata type 1 2014-05-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000324320 SCV000460525 pathogenic PEX7-Related Disorders 2017-04-28 criteria provided, single submitter clinical testing The PEX7 c.120C>G (p.Tyr40Ter) variant is a stop-gained variant that has been reported in five individuals, including two compound heterozygotes diagnosed with Refsum disease, one compound heterozygote diagnosed with rhizomelic chondrodysplasia punctate (RCDP), and two heterozygotes diagnosed with RCDP in whom a second variant was not identified (Motley et al. 2002; van den Brink et al. 2003; Wood et al. 2014). Control data are unavailable for this variant, which it is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. In cultured skin fibroblasts from patients carrying the p.Tyr40Ter variant, van den Brink (2003) demonstrated that the variant leads to deficiency of phytanic acid alpha-oxidation, PhyH activity, and plasmalogen synthesis, defective subcellular localization, and an inability to restore thiolase protein transport, as compared to controls. Based on the evidence and the potential impact of stop-gained variants, the p.Tyr40Ter variant is classified as pathogenic for PEX7-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Integrated Genetics/Laboratory Corporation of America RCV000147254 SCV000696492 pathogenic Rhizomelic chondrodysplasia punctata type 1 2017-08-08 criteria provided, single submitter clinical testing Variant summary: The PEX7 c.120C>G (p.Tyr40X) variant results in a premature termination codon, predicted to cause a truncated or absent PEX7 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is absent in 5288 control chromosomes (indicated to be a low-quality site in ExAC). Multiple publications have cited the variant in affected individuals dx with RCDP1, however, it has been noted to also be found in Refsum Disease pts (van der Brink_2003). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely pathogenic/pathogenic." Taken together, this variant is classified as pathogenic.
Invitae RCV000008230 SCV000962112 pathogenic Peroxisome biogenesis disorder 9B 2018-08-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr40*) in the PEX7 gene. It is expected to result in an absent or disrupted protein product. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals affected with rhizomelic chondrodysplasia punctata Type 1 and Refsum disease (PMID: 11781871, 12522768, 12325024). ClinVar contains an entry for this variant (Variation ID: 7788). Loss-of-function variants in PEX7 are known to be pathogenic (PMID: 12325024, 20301447). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008230 SCV000028437 pathogenic Peroxisome biogenesis disorder 9B 2003-02-01 no assertion criteria provided literature only
OMIM RCV000147254 SCV000028438 pathogenic Rhizomelic chondrodysplasia punctata type 1 2003-02-01 no assertion criteria provided literature only

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