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_000156.6(GAMT):c.328-10C>T

CA9043721

328349 (ClinVar)

Gene: GAMT
Condition: guanidinoacetate methyltransferase deficiency
Inheritance Mode: Autosomal recessive inheritance
UUID: ad889bfe-3c65-45de-ad9e-df3f43794e92
Approved on: 2024-10-08
Published on: 2024-10-25

HGVS expressions

NM_000156.6:c.328-10C>T
NM_000156.6(GAMT):c.328-10C>T
NC_000019.10:g.1399597G>A
CM000681.2:g.1399597G>A
NC_000019.9:g.1399596G>A
CM000681.1:g.1399596G>A
NC_000019.8:g.1350596G>A
NG_009785.1:g.6957C>T
ENST00000252288.8:c.328-10C>T
ENST00000447102.8:c.328-10C>T
ENST00000591788.3:c.11-10C>T
ENST00000640164.1:n.151C>T
ENST00000640762.1:c.259-10C>T
ENST00000252288.6:c.328-10C>T
ENST00000447102.7:c.328-10C>T
ENST00000591788.2:c.13-10C>T
NM_000156.5:c.328-10C>T
NM_138924.2:c.328-10C>T
NM_138924.3:c.328-10C>T
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Uncertain Significance

Met criteria codes 2
PM2 BP4

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 GAMT Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cerebral Creatine Deficiency Syndromes VCEP
The NM_000156.6:c.328-10C>T variant in GAMT is an intronic variant affecting a nucleotide within the consensus splice site of intron 2. To our knowledge, this variant has not been reported in the literature among individuals with GAMT deficiency and results of functional studies are unavailable. The highest population minor allele frequency in gnomAD v4.1.0. is 0.0003385 (10/29542 alleles) in the Ashkenazi Jewish population, followed by 0.0001857 (219/1179100) in the European non-Finnish population, both of which are lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.03 for acceptor loss suggesting that the variant has no impact on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 328349). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for GAMT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 2.0.0): PM2_Supporting, BP4. (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on October 8th, 2024).
Met criteria codes
PM2
The highest population minor allele frequency in gnomAD v4.1.0. is 0.0003385 (10/29542 alleles) in the Ashkenazi Jewish population, followed by 0.0001857 (219/1179100) in the European non-Finnish population, both of which are lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting).
BP4
The computational splicing predictor SpliceAI gives a score of 0.03 for acceptor loss suggesting that the variant has no impact on splicing (BP4).
Curation History
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