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]

Variant: NM_001482.3(GATM):c.1231G>A (p.Asp411Asn)

CA7542755

625953 (ClinVar)

Gene: GATM
Condition: AGAT deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 31671173-ebde-40de-9c16-a9912e852757
Approved on: 2022-06-06
Published on: 2022-10-07

HGVS expressions

NM_001482.3:c.1231G>A
NM_001482.3(GATM):c.1231G>A (p.Asp411Asn)
NC_000015.10:g.45362150C>T
CM000677.2:g.45362150C>T
NC_000015.9:g.45654348C>T
CM000677.1:g.45654348C>T
NC_000015.8:g.43441640C>T
NG_011674.1:g.21633G>A
NG_011674.2:g.45168G>A
ENST00000396659.8:c.1231G>A
ENST00000674905.1:c.*193G>A
ENST00000675158.1:c.*131G>A
ENST00000675323.1:c.*1733G>A
ENST00000675701.1:c.1171G>A
ENST00000675974.1:n.3780G>A
ENST00000676090.1:c.*1962G>A
ENST00000396659.7:c.1231G>A
ENST00000558362.5:n.2887G>A
NM_001482.2:c.1231G>A
NM_001321015.1:c.844G>A
NM_001321015.2:c.844G>A
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Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 2
BP4 PP3

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_001482.3: c.1231G>A variant in GATM is a missense variant predicted to cause substitution of aspartate by asparagine at amino acid 411 (p.Asp411Asn). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003 (3/112812 alleles) in the non-Finnish European population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.000055), meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.477 which is neither above nor below the thresholds predicting a damaging (>0.75) or benign (<0.15) impact on AGAT function. There is a ClinVar entry for this variant (Variation ID: 625953). In summary, this variant meets the criteria to be classified as a variant of uncertain significance 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): PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).
Met criteria codes
PM2_Supporting
The highest population minor allele frequency in gnomAD v2.1.1 is 0.000027 (3/112812 alleles) in non-Finnish Europeans.
Not Met criteria codes
BP4
The computational predictor REVEL gives a score of 0.477 which is neither above nor below the thresholds predicting a damaging (>0.75) or benign (<0.15) impact on AGAT function.
PP3
The computational predictor REVEL gives a score of 0.477 which is neither above nor below the thresholds predicting a damaging (>0.75) or benign (<0.15) impact on AGAT function.
Curation History
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