NM_001482.3(GATM):c.*27C>G AND Arginine:glycine amidinotransferase deficiency

Germline classification:: Benign (2 submissions)
Last evaluated:: Jun 6, 2022
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000355804.7

Allele description [Variation Report for NM_001482.3(GATM):c.*27C>G]

NM_001482.3(GATM):c.*27C>G

Gene:

GATM:glycine amidinotransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_001482.3(GATM):c.*27C>G

HGVS:

NC_000015.10:g.45362082G>C
NG_011674.2:g.45236C>G
NM_001321015.2:c.*27C>G
NM_001482.3:c.*27C>GMANE SELECT
NC_000015.9:g.45654280G>C
NM_001482.2:c.*27C>G

Links:

dbSNP: rs200143728

NCBI 1000 Genomes Browser:

rs200143728

Molecular consequence:

NM_001321015.2:c.*27C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001482.3:c.*27C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]

Condition(s)

Name:: Arginine:glycine amidinotransferase deficiency (CCDS3)
Synonyms:: AGAT deficiency; Creatine deficiency syndrome due to AGAT deficiency; GATM deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012996; MedGen: C2675179; Orphanet: 35704; OMIM: 612718

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000391422	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV002600093	ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen_CCDS_ACMG_Specifications_GATM_v1.1)	Benign (Jun 6, 2022)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000391422

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 12, 2018)

germline

clinical testing

Citation Link,

SCV002600093

ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen_CCDS_ACMG_Specifications_GATM_v1.1)

Benign
(Jun 6, 2022)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000391422.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen, SCV002600093.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The NM_001482.3:c.*27C>G variant is a single nucleotide substitution in the 3'UTR of GATM. Because the variant is located in the 3'UTR, it is not expected to alter the amino acid sequence. The highest population minor allele frequency in gnomAD v2.1.1 is 0.000856 (110/128560 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). There is a ClinVar entry for this variant (Variation ID: 316209). 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. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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