Submissions for variant NM_000466.3(PEX1):c.3767+2T>C

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002838198	SCV003216085	pathogenic	Zellweger spectrum disorders	2023-05-08	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 23 of the PEX1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PEX1 protein in which other variant(s) (Deletion of Exon 24) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Variants that disrupt 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 may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 2009222). This variant has not been reported in the literature in individuals affected with PEX1-related conditions. This variant is not present in population databases (gnomAD no frequency).