9-129095435-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000755.5(CRAT):c.1843C>T(p.Arg615Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,612,770 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. R615H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000755.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRAT | NM_000755.5 | c.1843C>T | p.Arg615Cys | missense_variant | 14/14 | ENST00000318080.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRAT | ENST00000318080.7 | c.1843C>T | p.Arg615Cys | missense_variant | 14/14 | 1 | NM_000755.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249662Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135416
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1460572Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 726618
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 615 of the CRAT protein (p.Arg615Cys). This variant is present in population databases (rs143822726, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CRAT-related conditions. 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) performed at Invitae indicates that this missense variant is not expected to disrupt CRAT 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at