Variant: NM_000156.6(GAMT):c.182G>A (p.Gly61Glu)

CA9043773

328350 (ClinVar)

Gene: GAMT

Condition: guanidinoacetate methyltransferase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 408d8d2d-1208-4609-be20-db6b5a9764d6

Approved on: 2025-03-18

Published on: 2025-03-20

HGVS expressions

NM_000156.6:c.182G>A
NM_000156.6(GAMT):c.182G>A (p.Gly61Glu)
NC_000019.10:g.1399938C>T
CM000681.2:g.1399938C>T
NC_000019.9:g.1399937C>T
CM000681.1:g.1399937C>T
NC_000019.8:g.1350937C>T
NG_009785.1:g.6616G>A
ENST00000252288.8:c.182G>A
ENST00000447102.8:c.182G>A
ENST00000640762.1:c.113G>A
ENST00000252288.6:c.182G>A
ENST00000447102.7:c.182G>A
NM_000156.5:c.182G>A
NM_138924.2:c.182G>A
NM_138924.3:c.182G>A

Benign

• Met criteria codes: BA1

• Not Met criteria codes: PM5

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.182G>A variant in GAMT is a missense variant that is predicted to cause the substitution of a glycine by a glutamate at amino acid position 61 (p.Gly61Glu). 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 (95% confidence) in gnomAD v4.1.0. is 0.01102 in the East Asian population, including 6 homozygotes. This is higher than the ClinGen CCDS VCEP threshold for BA1 (>0.003), meeting this criterion (BA1). There is a ClinVar entry for this variant (Variation ID: 328350). In summary, this variant meets the criteria to be classified as benign for GAMT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 2.0.0): BA1. (Classification approved by the ClinGen Cerebral Creatine Deficiencies Variant Curation Expert Panel on March 18, 2025)

Met criteria codes

• BA1: The GrpMax filtering allele frequency in gnomAD v4.1.0. is 0.01102 in the East Asian population, including 6 homozygotes. This is higher than the ClinGen CCDS VCEP threshold for BA1 (>0.003), meeting this criterion (BA1).

Not Met criteria codes

• PM5: c.181G>A (p.Gly61Arg) (ClinVar ID: 1098275) is likely path in ClinVar by 2 labs but not by the CCDS VCEP