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]

Variant: NM_000156.6(GAMT):c.279C>T (p.Asp93=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA291015

137434 (ClinVar)

Gene: GAMT

Condition: guanidinoacetate methyltransferase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3ce763f1-6ff6-44c9-8764-99f198f14dc1

Approved on: 2022-06-06

Published on: 2022-10-07

HGVS expressions

NM_000156.6:c.279C>T

NM_000156.6(GAMT):c.279C>T (p.Asp93=)

NC_000019.10:g.1399841G>A

CM000681.2:g.1399841G>A

NC_000019.9:g.1399840G>A

CM000681.1:g.1399840G>A

NC_000019.8:g.1350840G>A

NG_009785.1:g.6713C>T

ENST00000252288.8:c.279C>T

ENST00000447102.8:c.279C>T

ENST00000640762.1:c.210C>T

ENST00000252288.6:c.279C>T

ENST00000447102.7:c.279C>T

NM_000156.5:c.279C>T

NM_138924.2:c.279C>T

NM_138924.3:c.279C>T

Benign

BA1 BP7 BP4

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cerebral Creatine Deficiency Syndromes VCEP

The NM_000156.6:c.279C>T (p.Asp93=) is a synonymous variant in GAMT that is predicted to not impact splicing by SpliceAI and VarSeak, and the nucleotide is not highly conserved (BP4, BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00484 (87/17976 alleles) in the East Asian population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.003), and therefore meets this criterion (BA1). This variant does not appear to have been previously reported in the published literature. It is noted in ClinVar (Variation ID 137434). In summary, this variant meets the criteria to be classified as benign for GAMT deficiency. GAMT-specific ACMG/AMP codes met, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): BA1, BP4, BP7. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).

BA1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.00484 (87/17976 alleles) in the East Asian population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.003), and therefore meets this criterion (BA1).

BP7

It is predicted to not impact splicing by SpliceAI and VarSeak, and the nucleotide is not highly conserved (GERP rejected substitutions (RS) score -7.09) (BP7).

BP4

This variant is predicted to not impact splicing by SpliceAI and VarSeak BP4).

Curation History

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