15-45363953-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001482.3(GATM):c.1106G>A(p.Arg369His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001482.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GATM | NM_001482.3 | c.1106G>A | p.Arg369His | missense_variant | Exon 8 of 9 | ENST00000396659.8 | NP_001473.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251168Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135774
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461424Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 727032
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:1
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Arginine:glycine amidinotransferase deficiency Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 369 of the GATM protein (p.Arg369His). This variant is present in population databases (rs747557239, gnomAD 0.02%). 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: 498635). Invitae Evidence 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 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 GATM 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. -
Arginine:glycine amidinotransferase deficiency;C4551503:Fanconi renotubular syndrome 1 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at