Submissions for variant NM_000530.8(MPZ):c.68-1G>C

dbSNP: rs1057518021

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000412954	SCV000491374	pathogenic	not provided	2015-12-30	criteria provided, single submitter	clinical testing	The c.68-1 G>C splice site variant in the MPZ gene destroys the canonical splice acceptor site in intron 1. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, this substitution occurs at a position that is conserved across species.
Invitae	RCV003741178	SCV004458847	likely pathogenic	Charcot-Marie-Tooth disease, type I	2023-04-25	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 372846). This variant has not been reported in the literature in individuals affected with MPZ-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 1 of the MPZ gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MPZ are known to be pathogenic (PMID: 14711881).