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Variant: NM_001482.3(GATM):c.1239G>A (p.Arg413=)

CA291041

137451 (ClinVar)

Gene: GATM
Condition: AGAT deficiency
Inheritance Mode: Autosomal recessive inheritance
UUID: 96bc7f90-9bd0-4569-be73-e8698ead0b8e
Approved on: 2022-06-06
Published on: 2022-10-07

HGVS expressions

NM_001482.3:c.1239G>A
NM_001482.3(GATM):c.1239G>A (p.Arg413=)
NC_000015.10:g.45362142C>T
CM000677.2:g.45362142C>T
NC_000015.9:g.45654340C>T
CM000677.1:g.45654340C>T
NC_000015.8:g.43441632C>T
NG_011674.1:g.21641G>A
NG_011674.2:g.45176G>A
ENST00000396659.8:c.1239G>A
ENST00000674905.1:c.*201G>A
ENST00000675158.1:c.*139G>A
ENST00000675323.1:c.*1741G>A
ENST00000675701.1:c.1179G>A
ENST00000675974.1:n.3788G>A
ENST00000676090.1:c.*1970G>A
ENST00000396659.7:c.1239G>A
ENST00000558362.5:n.2895G>A
NM_001482.2:c.1239G>A
NM_001321015.1:c.852G>A
NM_001321015.2:c.852G>A
More

Benign

Met criteria codes 3
BP4 BP7 BA1

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.1239G>A (p.Arg413=) variant in GATM is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by PhyloP (BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00102 (36/35408 alleles) in the Latino population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.0005), and therefore meets this criterion (BA1). The computational splicing predictor SpliceAI gives a score of 0.0 for donor and acceptor loss suggesting that the variant has no impact on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 137451) with 2 submitters classifying the variant as benign/likely benign. In summary, this variant meets the criteria to be classified as 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): BA1, BP4, BP7. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).
Met criteria codes
BP4
No predicted impact on splicing by SpliceAI and varSEAK (BP4).
BP7
Not conserved nucleotide, not predicted to affect splicing (BP7).
BA1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00102 (36/35408 alleles) in the Latino population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.0005), and therefore meets this criterion (BA1).
Curation History
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