9-129095492-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000755.5(CRAT):c.1786G>A(p.Ala596Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,384 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A596V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000755.5 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 |
---|---|---|---|---|---|---|---|---|
CRAT | NM_000755.5 | c.1786G>A | p.Ala596Thr | missense_variant | Exon 14 of 14 | ENST00000318080.7 | NP_000746.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000440 AC: 11AN: 250150Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135660
GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461172Hom.: 0 Cov.: 32 AF XY: 0.0000647 AC XY: 47AN XY: 726902
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1786G>A (p.A596T) alteration is located in exon 14 (coding exon 14) of the CRAT gene. This alteration results from a G to A substitution at nucleotide position 1786, causing the alanine (A) at amino acid position 596 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 596 of the CRAT protein (p.Ala596Thr). This variant is present in population databases (rs775660177, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CRAT-related conditions. ClinVar contains an entry for this variant (Variation ID: 2190140). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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