Variant: NM_000156.6(GAMT):c.459+9_459+12del

CA9043657

513151 (ClinVar)

Gene: GAMT

Condition: guanidinoacetate methyltransferase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 5834505d-cb7f-43d9-b1d9-ee4371ee18dc

Approved on: 2024-09-11

Published on: 2024-09-12

HGVS expressions

NM_000156.6:c.459+9_459+12del
NM_000156.6(GAMT):c.459+9_459+12del
NC_000019.10:g.1399119_1399122del
CM000681.2:g.1399119_1399122del
NC_000019.9:g.1399118_1399121del
CM000681.1:g.1399118_1399121del
NC_000019.8:g.1350118_1350121del
NG_009785.1:g.7435_7438del
ENST00000252288.8:c.459+9_459+12del
ENST00000447102.8:c.459+9_459+12del
ENST00000591788.3:c.142+9_142+12del
ENST00000640164.1:n.292+9_292+12del
ENST00000640762.1:c.390+9_390+12del
ENST00000252288.6:c.459+9_459+12del
ENST00000447102.7:c.459+9_459+12del
ENST00000591788.2:c.144+9_144+12del
NM_000156.5:c.459+9_459+12del
NM_138924.2:c.459+9_459+12del
NM_138924.3:c.459+9_459+12del

Uncertain Significance

• Met criteria codes: PM2_Supporting BP4

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 2.0.0

Evidence submitted by expert panel

Cerebral Creatine Deficiency Syndromes VCEP

The NM_000156.6:c.459+9_459+12del variant in GAMT is an intronic variant in intron 4 and leads to a deletion of 4 base pairs. To our knowledge, this variant has not been reported in the literature and results of functional studies are unavailable. The highest population minor allele frequency in gnomAD v4.1.0. is 0.00005330 (4/75046 alleles; no homozygotes) in the African/African American population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). The computational predictor SpliceAI suggests that this variant has no impact on the gene/gene product (score <0.1) (BP4). There is a ClinVar entry for the variant (Variation ID: 513151). Due to conflicting evidence, this variant is classified as a variant of unknown significance for GAMT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 2.0.0): BP4, PM2_Supporting. (Classification approved by the ClinGen Creatine Deficiency Syndromes Variant Curation Expert Panel on September 11, 2024).

Met criteria codes

• PM2_Supporting: The highest population minor allele frequency in gnomAD v4.1.0. is 0.00005330 (4/75046 alleles; no homozygotes) in the African/African American population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting)
• BP4: The computational predictor SpliceAI suggests that this variant has no impact on the gene/gene product (score <0.1) (BP4).