Submissions for variant NM_001482.3(GATM):c.69+13C>T

gnomAD frequency: 0.00101  dbSNP: rs573273215

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen	RCV000272571	SCV003852691	benign	Arginine:glycine amidinotransferase deficiency	2023-01-25	reviewed by expert panel	curation	The NM_001482.3:c.69+13C>T variant in GATM is an intronic variant located in intron 8. The highest population minor allele frequency in gnomAD v2.1.1 is 0.00151 (88/58242 alleles) in the non-Finnish European population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.0005), and therefore meets this criterion (BA1). The computational splicing predictor SpliceAI gives a score of 0.0 for donor and acceptor loss suggesting that the variant has no impact on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 137454). In summary, this variant meets the criteria to be classified as benign for AGAT 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): BA1, BP4. (Classification approved by the ClinGen CCDS VCEP on January 25, 2023).
GeneDx	RCV000125214	SCV000168655	benign	not specified	2013-06-21	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.
Illumina Laboratory Services, Illumina	RCV000272571	SCV000391429	uncertain significance	Arginine:glycine amidinotransferase deficiency	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000272571	SCV002394855	likely benign	Arginine:glycine amidinotransferase deficiency	2024-01-29	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000272571	SCV000733461	likely benign	Arginine:glycine amidinotransferase deficiency		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001699126	SCV001920021	likely benign	not provided		no assertion criteria provided	clinical testing