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


Variant: NM_000156.6(GAMT):c.707G>C (p.Gly236Ala)

CA314836

205596 (ClinVar)

Gene: GAMT
Condition: guanidinoacetate methyltransferase deficiency
Inheritance Mode: Autosomal recessive inheritance
UUID: a778869a-1616-4c03-9bc3-f083a641b642
Approved on: 2022-06-06
Published on: 2022-10-07

HGVS expressions

NM_000156.6:c.707G>C
NM_000156.6(GAMT):c.707G>C (p.Gly236Ala)
NC_000019.10:g.1397363C>G
CM000681.2:g.1397363C>G
NC_000019.9:g.1397362C>G
CM000681.1:g.1397362C>G
NC_000019.8:g.1348362C>G
NG_008283.1:g.18480C>G
NG_009785.1:g.9191G>C
ENST00000252288.8:c.707G>C
ENST00000640762.1:c.638G>C
ENST00000252288.6:c.707G>C
NM_000156.5:c.707G>C

Uncertain Significance

Met criteria codes 2
BP4 PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Cerebral Creatine Deficiency Syndromes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GAMT Version 1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_000156.6:c.707G>C (p.Gly236Ala) variant in GAMT is a missense variant predicted to cause substitution of glycine by alanine at amino acid 236 (p.Gly236Ala). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00015 (19/126040 alleles) in the European non-Finnish population, which is lower than the ClinGen CCDS VCEP's threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.323 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAMT function (BP4). To our knowledge, this variant has not been reported in the published literature. This variant is noted in ClinVar (ID 205596). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for GAMT deficiency. GAMT-specific ACMG/AMP codes met, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes VCEP (Specifications Version 1.1.00): PM2_Supporting, BP4. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).
Met criteria codes
BP4
The computational predictor REVEL gives a score of 0.323 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAMT function (BP4).
PM2_Supporting
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00015 (19/126040) in the European non-Finnish population, which is lower than the ClinGen CCDS VCEP's threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting).
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