chr19-1401438-G-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_000156.6(GAMT):c.39C>A(p.Gly13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000333 in 1,412,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★). Synonymous variant affecting the same amino acid position (i.e. G13G) has been classified as Likely benign.
Frequency
Consequence
NM_000156.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAMT | NM_000156.6 | c.39C>A | p.Gly13= | synonymous_variant | 1/6 | ENST00000252288.8 | |
GAMT | NM_138924.3 | c.39C>A | p.Gly13= | synonymous_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAMT | ENST00000252288.8 | c.39C>A | p.Gly13= | synonymous_variant | 1/6 | 1 | NM_000156.6 | P1 | |
GAMT | ENST00000447102.8 | c.39C>A | p.Gly13= | synonymous_variant | 1/5 | 2 | |||
GAMT | ENST00000640762.1 | c.39C>A | p.Gly13= | synonymous_variant | 1/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152056Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000357 AC: 45AN: 1260138Hom.: 0 Cov.: 31 AF XY: 0.0000324 AC XY: 20AN XY: 617538
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74274
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 10, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Cerebral creatine deficiency syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Deficiency of guanidinoacetate methyltransferase Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen | Jun 06, 2022 | The NM_000156.6:c.39C>A (p.Gly13=) variant in GAMT is a synonymous variant in exon 1. It is absent in gnomAD v2.1.1 (PM2_Supporting); however, this region has low coverage and, therefore, the allele frequency data may not be accurate. It is predicted to not impact splicing by SpliceAI and VarSeak, and the nucleotide is not highly conserved (BP4, BP7). This variant does not appear to have been reported in the published literature. It is noted in ClinVar (Variation ID: 544263). Although this variant may be rare, it has been classified as likely benign by the ClinGen Creatine Deficiency Syndromes (CCDS) Variant Curation Expert Panel (VCEP) based on the recommendation of Richards et al (PMID: 25741868) because it is a synonymous variant, the altered nucleotide is not highly conserved, computational prediction suggests no impact on splicing, and there is no additional evidence to suggest that the variant is disease-causing. GAMT-specific ACMG/AMP criteria applied, as specified by the CCDS VCEP (Specifications Version 1.1.0): PM2_Supporting, BP4, BP7. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at