ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.570+161T>A

gnomAD frequency: 0.00035  dbSNP: rs368296913
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
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen RCV000767984 SCV005619908 likely benign Deficiency of guanidinoacetate methyltransferase 2024-09-11 reviewed by expert panel curation The NM_000156.6:c.570+161T>A variant in GAMT is an intronic variant affecting a nucleotide within the consensus splice site of intron 5. To our knowledge, this variant has not been reported in the literature and results of functional studies are unavailable. The highest population frequency in gnomAD v4.1.0. is 0.001162 (85/73150 alleles; no homozygotes) in the African / African American population, which is higher than the ClinGen CCDS VCEP’s threshold for BS1 (>0.001), and therefore meets this criterion (BS1). The computational splicing predictor SpliceAI gives a score of 0.0 for donor loss and suggests that the variant has no impact on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 625952). In summary, this variant meets the criteria to be classified as likely benign for GAMT deficiency. GAMT-specific ACMG/AMP codes met, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes VCEP (Specifications Version 2.0.0): BS1, BP4. (Classification approved by the ClinGen Creatine Deficiency Syndromes Variant Curation Expert Panel on September 11, 2024).
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767984 SCV000898727 uncertain significance Deficiency of guanidinoacetate methyltransferase 2021-03-30 criteria provided, single submitter clinical testing GAMT NM_138924 exon5 p.Leu244Gln (c.731T>A): This variant has not been reported in the literature but is present in 0.1% (25/16114) of Ashkenazi Jewish individuals in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs368296913). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
PreventionGenetics, part of Exact Sciences RCV003955495 SCV004776094 likely benign GAMT-related disorder 2022-02-23 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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.