Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002305515 | SCV002600147 | uncertain significance | Deficiency of guanidinoacetate methyltransferase | 2024-09-11 | reviewed by expert panel | curation | The NM_000156.6:c.459+9_459+12del variant in GAMT is an intronic variant in intron 4 and leads to a deletion of 4 base pairs. To our knowledge, this variant has not been reported in the literature and results of functional studies are unavailable. The highest population minor allele frequency in gnomAD v4.1.0. is 0.00005330 (4/75046 alleles; no homozygotes) in the African/African American population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). The computational predictor SpliceAI suggests that this variant has no impact on the gene/gene product (score <0.1) (BP4). There is a ClinVar entry for the variant (Variation ID: 513151). Due to conflicting evidence, this variant is classified as a variant of unknown significance for GAMT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 2.0.0): BP4, PM2_Supporting. (Classification approved by the ClinGen Creatine Deficiency Syndromes Variant Curation Expert Panel on September 11, 2024). |
Gene |
RCV000601307 | SCV000724378 | likely benign | not specified | 2017-11-06 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Labcorp Genetics |
RCV001398453 | SCV001600223 | likely benign | Cerebral creatine deficiency syndrome | 2025-01-20 | criteria provided, single submitter | clinical testing |