rs141807337
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_152743.4(BRAT1):c.1267G>C(p.Val423Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,605,564 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. V423I) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.1267G>C | p.Val423Leu | missense_variant | 9/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.1267G>C | p.Val423Leu | missense_variant | 9/14 | 1 | NM_152743.4 | P1 | |
BRAT1 | ENST00000467558.5 | n.1549G>C | non_coding_transcript_exon_variant | 7/10 | 5 | ||||
BRAT1 | ENST00000469750.5 | n.2749G>C | non_coding_transcript_exon_variant | 7/11 | 2 | ||||
BRAT1 | ENST00000493232.5 | n.2668G>C | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152188Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000298 AC: 7AN: 235074Hom.: 0 AF XY: 0.00000770 AC XY: 1AN XY: 129816
GnomAD4 exome AF: 0.00000963 AC: 14AN: 1453376Hom.: 1 Cov.: 33 AF XY: 0.00000415 AC XY: 3AN XY: 723330
GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152188Hom.: 1 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74344
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 423 of the BRAT1 protein (p.Val423Leu). This variant is present in population databases (rs141807337, gnomAD 0.05%). 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: 650361). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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