ClinVar Miner

Submissions for variant NM_018297.4(NGLY1):c.1405C>T (p.Arg469Ter)

gnomAD frequency: 0.00003  dbSNP: rs768131676
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000578540 SCV000680959 pathogenic not provided 2022-10-14 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 32071843, 34939090, 32395402, 26795593, 31497478, 28330790)
Ambry Genetics RCV000622683 SCV000740788 pathogenic Inborn genetic diseases 2021-11-24 criteria provided, single submitter clinical testing The c.1405C>T (p.R469*) alteration, located in exon 9 (coding exon 9) of the NGLY1 gene, consists of a C to T substitution at nucleotide position 1405. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 469. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of <0.01% (5/251086) total alleles studied. The highest observed frequency was 0.02% (3/18388) of East Asian alleles. This alteration has been identified as homozygous in multiple unrelated individuals with NGLY1-related congenital disorder of deglycosylation (Helbig, 2016; Chang, 2019). Based on the available evidence, this alteration is classified as pathogenic.
Invitae RCV000651488 SCV000773340 pathogenic Congenital disorder of deglycosylation 2023-11-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg469*) in the NGLY1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NGLY1 are known to be pathogenic (PMID: 24651605). This variant is present in population databases (rs768131676, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with epilepsy and autism spectrum disorder (PMID: 26795593, 28330790). ClinVar contains an entry for this variant (Variation ID: 488990). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.