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_138924.3:c.170C>A

CA402998003

Gene: GAMT

Condition: guanidinoacetate methyltransferase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 98e91684-332d-4be2-9e1f-850e4726e4a8

HGVS expressions

NM_138924.3:c.170C>A

NC_000019.10:g.1401307G>T

CM000681.2:g.1401307G>T

NC_000019.9:g.1401306G>T

CM000681.1:g.1401306G>T

NC_000019.8:g.1352306G>T

NG_009785.1:g.5247C>A

ENST00000252288.8:c.170C>A

ENST00000447102.8:c.170C>A

ENST00000640762.1:c.112+58C>A

ENST00000252288.6:c.170C>A

ENST00000447102.7:c.170C>A

NM_000156.5:c.170C>A

NM_138924.2:c.170C>A

NM_000156.6:c.170C>A

Uncertain Significance

PP3 PM2_Supporting

PM5

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

The NM_000156.6:c.170C>A (p.Ala57Asp) variant in GAMT has not been previously reported in individuals with guanidinoacetate methyltransferase deficiency or in ClinVar. This variant is absent from population databases (PM2_Supporting). The p.Ala57Asp variant is a missense variant that is predicted damaging by in-silico missense predictors (REVEL score 0.76) (PP3). In summary, the clinical significance of the p.Ala57Asp variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiencies Variant Curation Expert Panel (CCDS VCEP) (Specifications version 1.1.0): PM2_Supporting, PP3. (Classification approved by the ClinGen CCDS VCEP on March 23, 2023)

PP3

REVEL score 0.76, >0.75 cutoff for use of PP3

PM2_Supporting

Absent in population databases

PM5

A different missense variant at the same amino acid residue, p.Ala57Val, has been previously reported as a VUS in ClinVar (ClinVar Variation ID: 835475)

Approved on: 2023-03-23

Published on: 2023-03-29

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