9-129095494-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000755.5(CRAT):c.1784G>T(p.Cys595Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000744 in 1,613,418 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 (★★). Synonymous variant affecting the same amino acid position (i.e. C595C) has been classified as Likely benign.
Frequency
Consequence
NM_000755.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRAT | NM_000755.5 | c.1784G>T | p.Cys595Phe | missense_variant | 14/14 | ENST00000318080.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRAT | ENST00000318080.7 | c.1784G>T | p.Cys595Phe | missense_variant | 14/14 | 1 | NM_000755.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000520 AC: 13AN: 250148Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135668
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461198Hom.: 0 Cov.: 32 AF XY: 0.0000825 AC XY: 60AN XY: 726926
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74366
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2022 | The c.1784G>T (p.C595F) alteration is located in exon 14 (coding exon 14) of the CRAT gene. This alteration results from a G to T substitution at nucleotide position 1784, causing the cysteine (C) at amino acid position 595 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 24, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with CRAT-related conditions. This variant is present in population databases (rs749869835, gnomAD 0.008%). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 595 of the CRAT protein (p.Cys595Phe). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at