7-2540996-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152743.4(BRAT1):c.1378C>T(p.Pro460Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,553,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P460L) has been classified as Uncertain significance.
Frequency
Consequence
NM_152743.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.1378C>T | p.Pro460Ser | missense_variant | 10/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.1378C>T | p.Pro460Ser | missense_variant | 10/14 | 1 | NM_152743.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000482 AC: 9AN: 186618Hom.: 0 AF XY: 0.0000865 AC XY: 9AN XY: 104020
GnomAD4 exome AF: 0.0000307 AC: 43AN: 1400964Hom.: 0 Cov.: 31 AF XY: 0.0000302 AC XY: 21AN XY: 696054
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74340
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 02, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 460 of the BRAT1 protein (p.Pro460Ser). This variant is present in population databases (rs373935601, gnomAD 0.009%). 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: 472938). 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 disruptive. 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