Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_000156.6(GAMT):c.655G>A (p.Asp219Asn)

CA314786

205569 (ClinVar)

Gene: GAMT
Condition: guanidinoacetate methyltransferase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 20230fce-2268-44ff-b7e7-2efcca6bf325
Approved on: 2024-09-11
Published on: 2024-09-12

HGVS expressions

NM_000156.6:c.655G>A
NM_000156.6(GAMT):c.655G>A (p.Asp219Asn)
NC_000019.10:g.1397415C>T
CM000681.2:g.1397415C>T
NC_000019.9:g.1397414C>T
CM000681.1:g.1397414C>T
NC_000019.8:g.1348414C>T
NG_008283.1:g.18532C>T
NG_009785.1:g.9139G>A
ENST00000252288.8:c.655G>A
ENST00000640164.1:n.488G>A
ENST00000640762.1:c.586G>A
ENST00000252288.6:c.655G>A
NM_000156.5:c.655G>A

Uncertain Significance

Not Met criteria codes 5
PP3 PM5 PM2 BS1 BP4

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 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_000156.6:c.655G>A variant in GAMT is a missense variant that is predicted to cause the substitution of aspartate for asparagine at amino acid 219 (p.Asp219Asn). To our knowledge, this variant has not been reported in the literature and results of functional studies are unavailable. The highest population minor allele frequency in gnomAD v4.1.0. is 0.0004834 (29/59986 alleles) in the Admixed American population (none of the population data codes are met). The computational predictor REVEL gives a score of 0.293 which is neither above nor below the thresholds predicting a damaging (>0.644) or benign (<0.29) impact on GAMT function. There is a ClinVar entry for this variant (Variation ID: 205569). 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 2.0.0): no criteria met. (Classification approved by the ClinGen Creatine Deficiency Syndromes Variant Curation Expert Panel on September 11, 2024).
Not Met criteria codes
PP3
The computational predictor REVEL gives a score of 0.293 which is neither above nor below the thresholds predicting a damaging (>0.644) or benign (<0.29) impact on GAMT function.
PM5
c.657C>A (p.Asp219Glu) is a VUS in ClinVar (ID: 1754277)
PM2
The highest population minor allele frequency in gnomAD v4.1.0. is 0.0004834 (29/59986 alleles) in the Admixed American population (none of the population data codes are met).
BS1
The highest population minor allele frequency in gnomAD v4.1.0. is 0.0004834 (29/59986 alleles) in the Admixed American population (none of the population data codes are met).
BP4
The computational predictor REVEL gives a score of 0.293 which is neither above nor below the thresholds predicting a damaging (>0.644) or benign (<0.29) impact on GAMT function.
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