ClinVar Miner

Submissions for variant NM_000030.3(AGXT):c.33dup (p.Lys12fs) (rs180177201)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000128800 SCV000678017 pathogenic Primary hyperoxaluria, type I 2015-10-09 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group,Broad Institute RCV000128800 SCV000786702 pathogenic Primary hyperoxaluria, type I criteria provided, single submitter research The homozgous c.33dupC variant was identified by our study in one individual with Hyperoxaluria. The c.33dupC is a well-established known pathogenic variant (https://www.ncbi.nlm.nih.gov/books/NBK1283/) and loss of function is a known mechanism of disease in the AGXT gene.
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000128800 SCV000891673 pathogenic Primary hyperoxaluria, type I 2017-12-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779688 SCV000916432 pathogenic Primary hyperoxaluria 2018-09-24 criteria provided, single submitter clinical testing Variant summary: AGXT c.33dupC (p.Lys12GlnfsX156) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00016 in 30572 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in AGXT causing Primary Hyperoxaluria Type 1 (0.00047 vs 0.0024), allowing no conclusion about variant significance. c.33dupC has been reported in the literature in a multiple affected individuals with Primary Hyperoxaluria Type 1 (Rumsby_2004, Mbarek_2017). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Rumsby 2004). A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000800941 SCV000940686 pathogenic not provided 2018-07-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys12Glnfs*156) in the AGXT gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This is one of the most common variants reported in individuals affected with primary hyperoxaluria (PMID: 15327387, 19479957, 25629080, 27135212). It is also known as 33_34insC in the literature. ClinVar contains an entry for this variant (Variation ID: 140583). Loss-of-function variants in AGXT are known to be pathogenic (PMID: 19479957). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000128800 SCV000172449 pathogenic Primary hyperoxaluria, type I 2014-07-17 no assertion criteria provided literature only
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000128800 SCV000239730 pathogenic Primary hyperoxaluria, type I 2014-11-27 no assertion criteria provided research

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.