7-2540990-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152743.4(BRAT1):āc.1384T>Cā(p.Ser462Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000644 in 1,552,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S462F) 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.1384T>C | p.Ser462Pro | missense_variant | 10/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.1384T>C | p.Ser462Pro | missense_variant | 10/14 | 1 | NM_152743.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152116Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000214 AC: 4AN: 186730Hom.: 0 AF XY: 0.0000288 AC XY: 3AN XY: 104016
GnomAD4 exome AF: 0.00000571 AC: 8AN: 1400340Hom.: 0 Cov.: 31 AF XY: 0.00000719 AC XY: 5AN XY: 695722
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152116Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74314
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2022 | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 462 of the BRAT1 protein (p.Ser462Pro). This variant is present in population databases (rs761704986, gnomAD 0.02%). 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: 540157). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | GeneDx | Sep 17, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at