Submissions for variant NM_032520.5(GNPTG):c.318-28_351del

dbSNP: rs2034895916

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001875771	SCV002184201	pathogenic	not provided	2021-09-02	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asn116 amino acid residue in GNPTG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15532026, 19370764, 29170090). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 917842). This variant has not been reported in the literature in individuals affected with GNPTG-related conditions. This variant is not present in population databases (ExAC no frequency). This variant results in the deletion of part of exon 6 (c.318-28_351del) of the GNPTG 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 GNPTG are known to be pathogenic (PMID: 19370764, 20301784).
Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS	RCV001175118	SCV001338697	likely pathogenic	GNPTG-mucolipidosis	2019-01-01	no assertion criteria provided	research