7-2538295-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152743.4(BRAT1):c.2240C>T(p.Ser747Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S747S) has been classified as Likely benign.
Frequency
Consequence
NM_152743.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.2240C>T | p.Ser747Phe | missense_variant | 14/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.2240C>T | p.Ser747Phe | missense_variant | 14/14 | 1 | NM_152743.4 | P1 | |
BRAT1 | ENST00000467558.5 | n.4026C>T | non_coding_transcript_exon_variant | 10/10 | 5 | ||||
BRAT1 | ENST00000469750.5 | n.4812C>T | non_coding_transcript_exon_variant | 11/11 | 2 | ||||
BRAT1 | ENST00000493232.5 | n.4946C>T | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460308Hom.: 0 Cov.: 62 AF XY: 0.00000413 AC XY: 3AN XY: 726502
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 28, 2021 | This sequence change replaces serine with phenylalanine at codon 747 of the BRAT1 protein (p.Ser747Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRAT1-related conditions. 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 C15"). 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