Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003461654 | SCV004227931 | pathogenic | Deficiency of guanidinoacetate methyltransferase | 2023-10-12 | reviewed by expert panel | curation | The NM_000156.6: c.235C>T (p.Gln79Ter) variant in GAMT is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 2/6 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been detected in at least one patient with GAMT deficiency. This individual was homozygous for the variant (PMIDs 32606564) (PM3_Supporting). The patient reported with this variant had elevated GAA in plasma and significantly decreased creatine peak (PP4_Strong). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for GAMT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0): PVS1, PP4_Strong, PM3_Supporting, PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP on Oct. 12, 2023) |
Baylor Genetics | RCV003461654 | SCV004198580 | pathogenic | Deficiency of guanidinoacetate methyltransferase | 2023-08-19 | criteria provided, single submitter | clinical testing |