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_001482.3(GATM):c.1269C>G (p.Asp423Glu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA392254551

589915 (ClinVar)

Gene: GATM

Condition: AGAT deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 59922c1f-f11d-4a37-947e-cbd65fe16ee8

Approved on: 2022-06-06

Published on: 2022-10-07

HGVS expressions

NM_001482.3:c.1269C>G

NM_001482.3(GATM):c.1269C>G (p.Asp423Glu)

NC_000015.10:g.45362112G>C

CM000677.2:g.45362112G>C

NC_000015.9:g.45654310G>C

CM000677.1:g.45654310G>C

NC_000015.8:g.43441602G>C

NG_011674.1:g.21671C>G

NG_011674.2:g.45206C>G

ENST00000396659.8:c.1269C>G

ENST00000674905.1:c.*231C>G

ENST00000675158.1:c.*169C>G

ENST00000675323.1:c.*1771C>G

ENST00000675701.1:c.1209C>G

ENST00000675974.1:n.3818C>G

ENST00000676090.1:c.*2000C>G

ENST00000396659.7:c.1269C>G

ENST00000558362.5:n.2925C>G

NM_001482.2:c.1269C>G

NM_001321015.1:c.882C>G

NM_001321015.2:c.882C>G

Uncertain Significance

BP4 PM2_Supporting

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 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.1269C>G variant in GATM is a missense variant predicted to cause substitution of aspartate by glutamate at amino acid 423 (p.Asp423Glu). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.092 which is below the threshold of 0.15, evidence that does not predict a damaging effect on AGAT function, and SpliceAI does not predict any impact in splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 58991). 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, BP4. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).

BP4

The computational predictor REVEL gives a score of 0.092 which is below the threshold of 0.15, evidence that does not predict a damaging effect on AGAT function, and SpliceAI does not predict any impact on splicing (BP4).

PM2_Supporting

Absent from gnomAD v2.1.1 (PM2_Supporting).

Curation History

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