Submissions for variant NM_001482.3(GATM):c.1006A>G (p.Thr336Ala)

dbSNP: rs1889422994

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen	RCV003159183	SCV003852696	uncertain significance	Arginine:glycine amidinotransferase deficiency	2023-01-24	reviewed by expert panel	curation	The NM_001482.3:c.1006A>G in GATM is a missense variant that is predicted to result in the substitution of threonine by alanine at amino acid 336 (p.Thr336Ala). The variant is absent in gnomAD v2.1.1. (PM2_Supporting). The computational predictor REVEL gives a score of 0.127 which is below the threshold of 0.15, evidence that does not predict a damaging effect on AGAT function (BP4). To our knowledge, this variant has not been reported in an individual with phenotypic features of AGAT deficiency. It has been reported as a single heterozygous variant segregating in a family autosomal dominant renal Fanconi syndrome and kidney failure (PMID: 29654216). However, classification with respect to this alternative disorder is outside the scope of this curation. There is a ClinVar entry for this variant (Variation ID: 917494). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for AGAT deficiency. GATM-specific ACMG/AMP criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): PS3_Supporting, PM2_Supporting, BP4. (Classification approved by the ClinGen CCDS VCEP on January 24, 2023).
Fulgent Genetics, Fulgent Genetics	RCV005012585	SCV005630788	likely pathogenic	Arginine:glycine amidinotransferase deficiency; Fanconi renotubular syndrome 1	2024-05-22	criteria provided, single submitter	clinical testing
OMIM	RCV001174510	SCV001337649	pathogenic	Fanconi renotubular syndrome 1	2020-06-11	no assertion criteria provided	literature only