rs750400556
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152743.4(BRAT1):c.1879G>A(p.Ala627Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000507 in 1,598,218 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. A627V) has been classified as Likely benign.
Frequency
Consequence
NM_152743.4 missense
Scores
Clinical Significance
Conservation
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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.1879G>A | p.Ala627Thr | missense_variant | 14/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.1879G>A | p.Ala627Thr | missense_variant | 14/14 | 1 | NM_152743.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000439 AC: 10AN: 227994Hom.: 0 AF XY: 0.0000316 AC XY: 4AN XY: 126520
GnomAD4 exome AF: 0.0000505 AC: 73AN: 1445994Hom.: 0 Cov.: 65 AF XY: 0.0000458 AC XY: 33AN XY: 719856
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 34 AF XY: 0.0000672 AC XY: 5AN XY: 74370
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 01, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 627 of the BRAT1 protein (p.Ala627Thr). This variant is present in population databases (rs750400556, gnomAD 0.008%). 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: 445473). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2023 | The c.1879G>A (p.A627T) alteration is located in exon 14 (coding exon 13) of the BRAT1 gene. This alteration results from a G to A substitution at nucleotide position 1879, causing the alanine (A) at amino acid position 627 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
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 11, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at