7-2543256-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152743.4(BRAT1):c.871G>A(p.Gly291Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,611,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. G291V) has been classified as Uncertain significance.
Frequency
Consequence
NM_152743.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.871G>A | p.Gly291Ser | missense_variant | 6/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.871G>A | p.Gly291Ser | missense_variant | 6/14 | 1 | NM_152743.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000964 AC: 24AN: 248900Hom.: 0 AF XY: 0.0000742 AC XY: 10AN XY: 134710
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1459288Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 725852
GnomAD4 genome AF: 0.000217 AC: 33AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74332
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 291 of the BRAT1 protein (p.Gly291Ser). This variant is present in population databases (rs764583480, gnomAD 0.07%). This missense change has been observed in individual(s) with clinical features of BRAT1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 540156). 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 BRAT1 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 19, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at