rs369580400
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The ENST00000396659.8(GATM):c.655G>A(p.Ala219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000396659.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GATM | NM_001482.3 | c.655G>A | p.Ala219Thr | missense_variant | 4/9 | ENST00000396659.8 | NP_001473.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GATM | ENST00000396659.8 | c.655G>A | p.Ala219Thr | missense_variant | 4/9 | 1 | NM_001482.3 | ENSP00000379895 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251364Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135862
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461828Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727216
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
Arginine:glycine amidinotransferase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 23, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 219 of the GATM protein (p.Ala219Thr). This variant is present in population databases (rs369580400, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 225917). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect GATM function (PMID: 27233232). 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. - |
not provided Other:1
not provided, no classification provided | in vitro | Hospital for Sick Children | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at