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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000156.6(GAMT):c.392-7C>T

CA291019

137436 (ClinVar)

Gene: GAMT

Condition: guanidinoacetate methyltransferase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1d2f0109-c759-48c0-b673-9beac50abf35

Approved on: 2022-06-06

Published on: 2022-10-07

HGVS expressions

NM_000156.6:c.392-7C>T

NM_000156.6(GAMT):c.392-7C>T

NC_000019.10:g.1399202G>A

CM000681.2:g.1399202G>A

NC_000019.9:g.1399201G>A

CM000681.1:g.1399201G>A

NC_000019.8:g.1350201G>A

NG_009785.1:g.7352C>T

ENST00000252288.8:c.392-7C>T

ENST00000447102.8:c.392-7C>T

ENST00000591788.3:n.75-7C>T

ENST00000640164.1:n.225-7C>T

ENST00000640762.1:c.323-7C>T

ENST00000252288.6:c.392-7C>T

ENST00000447102.7:c.392-7C>T

ENST00000591788.2:n.77-7C>T

NM_000156.5:c.392-7C>T

NM_138924.2:c.392-7C>T

NM_138924.3:c.392-7C>T

Benign

BA1 BS2 BP4

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 GAMT Version 1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cerebral Creatine Deficiency Syndromes VCEP

The NM_000156.6:c.392-7C>T variant in GAMT is a nucleotide substitution in intron 3. The highest population minor allele frequency in gnomAD v2.1.1 is 0.00430 (107/24892 alleles) in the African population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.003), and therefore meets this criterion (BA1). There are 4 homozygotes in gnomAD v2.1.1 (all in the S Asian population) which, given the early onset and severity of phenotype for GAMT deficiency, supporting that the variant is not associated with GAMT deficiency. Computational evidence from SpliceAI and varSEAK suggests no impact on the gene/gene product (BP4). There is a ClinVar entry for this variant (Variation ID: 137436,). In summary, this variant meets the criteria to be classified as Benign 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 1.1.0): BA1, BS2, BP4. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).

BA1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.00430 (107/24892 alleles) in the African population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.003), and therefore meets this criterion (BA1).

BS2

There are 4 homozygotes in gnomAD v2.1.1 (all in the S Asian population) which, given the early onset and severity of phenotype for GAMT deficiency, supports that this variant is benign.

BP4

The computational splicing predictor SpliceAI gives a score of 0.00 for acceptor loss suggesting that the variant has no impact on splicing (BP4).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.