rs758217156
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000156.6(GAMT):c.472C>T(p.Arg158Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000024 in 1,461,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000156.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAMT | NM_000156.6 | c.472C>T | p.Arg158Cys | missense_variant | 5/6 | ENST00000252288.8 | |
GAMT | NM_138924.3 | c.472C>T | p.Arg158Cys | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAMT | ENST00000252288.8 | c.472C>T | p.Arg158Cys | missense_variant | 5/6 | 1 | NM_000156.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250780Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135804
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1461132Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 726864
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cerebral creatine deficiency syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 158 of the GAMT protein (p.Arg158Cys). This variant is present in population databases (rs758217156, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with GAMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 544256). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GAMT protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Deficiency of guanidinoacetate methyltransferase Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at