Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001972702 | SCV002240673 | pathogenic | not provided | 2023-02-13 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PEX3-related conditions. This sequence change creates a premature translational stop signal (p.Trp6*) in the PEX3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX3 are known to be pathogenic (PMID: 10942428, 21031596). This variant is present in population databases (no rsID available, gnomAD 0.002%). ClinVar contains an entry for this variant (Variation ID: 1457724). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479376 | SCV004222946 | pathogenic | Peroxisome biogenesis disorder | 2023-11-20 | criteria provided, single submitter | clinical testing | Variant summary: PEX3 c.17G>A (p.Trp6X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 251346 control chromosomes. To our knowledge, no occurrence of c.17G>A in individuals affected with Zellweger Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |