7-2539852-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_152743.4(BRAT1):c.1432C>G(p.Leu478Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000967 in 1,447,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000890 AC: 2AN: 224844Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 122422
GnomAD4 exome AF: 0.00000967 AC: 14AN: 1447628Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 10AN XY: 719518
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRAT1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 478 of the BRAT1 protein (p.Leu478Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at