Submissions for variant NM_000286.3(PEX12):c.894del (p.Lys299_Met300insTer)

dbSNP: rs398123302

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078564	SCV000110420	pathogenic	not provided	2013-11-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000078564	SCV000330067	pathogenic	not provided	2015-12-17	criteria provided, single submitter	clinical testing	The c.894delC pathogenic variant in the PEX12 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant replaces the Methionine residue at position 300 with a premature Stop codon, denoted p.Met300Ter. This variant is predicted to cause loss of normal protein function through protein truncation. The c.894delC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common variant in these populations. We interpret c.894delC as a pathogenic variant.
Counsyl	RCV000669619	SCV000794390	likely pathogenic	Peroxisome biogenesis disorder type 3B; Peroxisome biogenesis disorder 3A (Zellweger)	2017-10-25	criteria provided, single submitter	clinical testing
Invitae	RCV001854382	SCV002181200	pathogenic	Peroxisome biogenesis disorder 3A (Zellweger)	2023-11-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Met300*) in the PEX12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 60 amino acid(s) of the PEX12 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of PEX12-related conditions (PMID: 27763634). ClinVar contains an entry for this variant (Variation ID: 92777). This variant disrupts a region of the PEX12 protein in which other variant(s) (p.Glu347Serfs*6) 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. For these reasons, this variant has been classified as Pathogenic.