Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000156.6(GAMT):c.79T>C (p.Tyr27His)

CA295620

167131 (ClinVar)

Gene: GAMT

Condition: guanidinoacetate methyltransferase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7c04e605-50d3-4535-babc-261b76fc7eee

Approved on: 2023-02-08

Published on: 2023-03-09

HGVS expressions

NM_000156.6:c.79T>C

NM_000156.6(GAMT):c.79T>C (p.Tyr27His)

NC_000019.10:g.1401398A>G

CM000681.2:g.1401398A>G

NC_000019.9:g.1401397A>G

CM000681.1:g.1401397A>G

NC_000019.8:g.1352397A>G

NG_009785.1:g.5156T>C

ENST00000252288.8:c.79T>C

ENST00000447102.8:c.79T>C

ENST00000640762.1:c.79T>C

ENST00000252288.6:c.79T>C

ENST00000447102.7:c.79T>C

NM_000156.5:c.79T>C

NM_138924.2:c.79T>C

NM_138924.3:c.79T>C

Benign

BS3_Supporting BA1

PP3

Evidence Links 0

Expert Panel

Cerebral Creatine Deficiency Syndromes VCEP

Criteria Specification Information

Criteria Specification: ClinGen Cerebral Creatine Deficiency Syndromes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GAMT Version 1.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cerebral Creatine Deficiency Syndromes VCEP

NM_000156.6:c.79T>C variant in GAMT is a missense variant that is predicted to result in the substitution of tyrosine by histidine at amino acid 27 (p.Tyr27His). This variant was identified in the homozygous state in an individual with normal GAMT enzyme activity in fibroblasts (PMID: 24415674). The variant is present in gnomAD v2.1.1. at a maximum population frequency of 0.00471 (>0.003, cutoff for BA1) and found in the homozygous state in 2 individuals in gnomAD v2.1.1 (BA1). In fibroblasts, overexpressing the GAMT c.79T>C (p.Tyr27His) variant, restored GAMT activity to similar levels as the wild-type GAMT transfection (PMID: 24415674)(BS3_Supporting). There is a ClinVar entry for this variant (Variation ID: 167131). In summary, this variant meets the criteria to be classified as benign for GAMT deficiency. GAMT-specific ACMG/AMP criteria met, based on the specifications of the ClinGen Cerebral Creatine Deficiencies VCEP (Specifications Version 1.1.0): BA1, BS3_Supporting. (Classification approved by the ClinGen CCDS VCEP on February 8, 2023).

BS3_Supporting

In fibroblasts, overexpressing the GAMT c.79T>C (p.Tyr27His) variant, restored GAMT activity to similar levels as the wild-type GAMT transfection.

BA1

gnomAD popmax AF 0.00471 (>0.003, cutoff for BA1)

PP3

REVEL score 0.652 (<0.75, cutoff for PP3)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.