rs141709461
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152743.4(BRAT1):c.1702G>A(p.Ala568Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000041 in 1,611,290 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A568A) has been classified as Likely benign.
Frequency
Consequence
NM_152743.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.1702G>A | p.Ala568Thr | missense_variant | 13/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.1702G>A | p.Ala568Thr | missense_variant | 13/14 | 1 | NM_152743.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000366 AC: 9AN: 245716Hom.: 0 AF XY: 0.0000523 AC XY: 7AN XY: 133824
GnomAD4 exome AF: 0.0000418 AC: 61AN: 1459068Hom.: 0 Cov.: 32 AF XY: 0.0000455 AC XY: 33AN XY: 725836
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 568 of the BRAT1 protein (p.Ala568Thr). This variant is present in population databases (rs141709461, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with BRAT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 573632). 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 | Athena Diagnostics | Jul 24, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at