The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_001482.3(GATM):c.277A>G (p.Ile93Val)

CA314862

205610 (ClinVar)

Gene: GATM
Condition: AGAT deficiency
Inheritance Mode: Autosomal recessive inheritance
UUID: 41225082-965c-449c-b75b-3d8941aabf03
Approved on: 2024-10-08
Published on: 2024-10-25

HGVS expressions

NM_001482.3:c.277A>G
NM_001482.3(GATM):c.277A>G (p.Ile93Val)
NC_000015.10:g.45376612T>C
CM000677.2:g.45376612T>C
NC_000015.9:g.45668810T>C
CM000677.1:g.45668810T>C
NC_000015.8:g.43456102T>C
NG_011674.1:g.7171A>G
NG_011674.2:g.30706A>G
ENST00000396659.8:c.277A>G
ENST00000674905.1:c.277A>G
ENST00000675158.1:c.277A>G
ENST00000675323.1:c.277A>G
ENST00000675701.1:c.217A>G
ENST00000675974.1:n.368A>G
ENST00000676090.1:c.436A>G
ENST00000396659.7:c.277A>G
ENST00000558118.1:c.277A>G
ENST00000558163.1:c.69+1773A>G
ENST00000558336.5:c.277A>G
ENST00000558362.5:n.1933A>G
ENST00000558537.5:c.-111A>G
ENST00000559885.1:c.-111A>G
ENST00000560538.1:n.546A>G
ENST00000561148.5:c.-111A>G
NM_001482.2:c.277A>G
NM_001321015.1:c.-111A>G
NM_001321015.2:c.-111A>G
More

Likely Benign

Met criteria codes 2
BS1 BP4
Not Met criteria codes 3
BS3 PS3 PM5

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 GATM Version 1.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_001482.3:c.277A>G variant in GATM is a missense variant that is predicted to cause the substitution of an isoleucine by a valine at amino acid position 93 (p.Ile93Val). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00012 (2/16256 alleles) in the African population, which is higher than the ClinGen CCDS VCEP’s threshold for BS1 (>0.0001), and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.143 which is below the threshold of 0.15, evidence that does not predict a damaging effect on AGAT function (BP4). Expression of the variant in HeLa cells resulted in 18% of wild type AGAT activity, over than the cutoff for PS3_Supporting (<15%) and less than the cutoff for BS3_Supporting (≥30%), such that no experimental evidence codes are met. There is a ClinVar entry for this variant (Variation ID: 205610). In summary, this variant meets the criteria to be classified as likely benign for AGAT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0): BS1, BP4. (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on October 8th, 2024).
Met criteria codes
BS1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00012 (2/16256 alleles) in the African population, which is higher than the ClinGen CCDS VCEP’s threshold for BS1 (>0.0001), and therefore meets this criterion (BS1).
BP4
The computational predictor REVEL gives a score of 0.143 which is below the threshold of 0.15, evidence that does not predict a damaging effect on AGAT function (BP4).
Not Met criteria codes
BS3
Expression of the variant in HeLa cells resulted in 18% of wild type AGAT activity, over than the cutoff for PS3_Supporting (<15%) and less than the cutoff for BS3_Supporting (≥30%), such that no experimental evidence codes are met.
PS3
Expression of the variant in HeLa cells resulted in 18% of wild type AGAT activity, over than the cutoff for PS3_Supporting (<15%) and less than the cutoff for BS3_Supporting (≥30%), such that no experimental evidence codes are met.
PM5
c.279C>G (p.Ile93Met) is classified as a VUS in ClinVar (ID: 205611)
Curation History
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