Variant: NM_000156.6(GAMT):c.242C>T (p.Ala81Val)

CA314796

205576 (ClinVar)

Gene: GAMT

Condition: guanidinoacetate methyltransferase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 8c49348d-c98b-4011-89fe-173d3aab2af0

Approved on: 2025-03-18

Published on: 2025-03-20

HGVS expressions

NM_000156.6:c.242C>T
NM_000156.6(GAMT):c.242C>T (p.Ala81Val)
NC_000019.10:g.1399878G>A
CM000681.2:g.1399878G>A
NC_000019.9:g.1399877G>A
CM000681.1:g.1399877G>A
NC_000019.8:g.1350877G>A
NG_009785.1:g.6676C>T
ENST00000252288.8:c.242C>T
ENST00000447102.8:c.242C>T
ENST00000640762.1:c.173C>T
ENST00000252288.6:c.242C>T
ENST00000447102.7:c.242C>T
NM_000156.5:c.242C>T
NM_138924.2:c.242C>T
NM_138924.3:c.242C>T

Likely Benign

• Met criteria codes: BS1 BP4

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 2.0.0

Evidence submitted by expert panel

Cerebral Creatine Deficiency Syndromes VCEP

The NM_000156.6:c.242C>T variant in GAMT is a missense variant that is predicted to cause the substitution of an alanine by a valine at amino acid position 81 (p.Ala81Val). To our knowledge, this variant has not been reported among individuals with GAMT deficiency and results of functional studies are unavailable. The GrpMax filtering allele frequency in gnomAD v4.1.0. is 0.001232 in the E. Asian population, which is higher than the ClinGen CCDS VCEP's threshold for BS1 (>0.001), and therefore meets this criterion. The computational predictor REVEL gives a score of 0.197 which is below the threshold of 0.29, evidence that does not predict a damaging effect on GAMT function (BP4). There is a ClinVar entry for this variant (Variation ID: 205576). In summary, this variant meets the criteria to be classified as likely benign for GAMT deficiency based on the GAMT-specific ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 2.0.0): BS1, BP4. (Classification approved by the ClinGen Cerebral Creatine Deficiencies Variant Curation Expert Panel on March 18, 2025)

Met criteria codes

• BS1: The GrpMax filtering allele frequency in gnomAD v4.1.0. is 0.001232 in the E. Asian population, which is higher than the ClinGen CCDS VCEP's threshold for BS1 (>0.001), and therefore meets this criterion.
• BP4: The computational predictor REVEL gives a score of 0.197 which is below the threshold of 0.29, evidence that does not predict a damaging effect on GAMT function. No impact on splicing predicted by SpliceAI (all scores <0.1) (BP4).