chr7-2538088-TC-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_152743.4(BRAT1):c.2446del(p.Asp816ThrfsTer65) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D816D) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
BRAT1
NM_152743.4 frameshift
NM_152743.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.974
Genes affected
BRAT1 (HGNC:21701): (BRCA1 associated ATM activator 1) The protein encoded by this ubiquitously expressed gene interacts with the tumor suppressing BRCA1 (breast cancer 1) protein and and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint signalling pathways that are required for cellular responses to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein complex BASC (BRAC1-associated genome surveillance complex). The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 887 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.2446del | p.Asp816ThrfsTer65 | frameshift_variant | 14/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.2446del | p.Asp816ThrfsTer65 | frameshift_variant | 14/14 | 1 | NM_152743.4 | P1 | |
BRAT1 | ENST00000467558.5 | n.4232del | non_coding_transcript_exon_variant | 10/10 | 5 | ||||
BRAT1 | ENST00000469750.5 | n.5018del | non_coding_transcript_exon_variant | 11/11 | 2 | ||||
BRAT1 | ENST00000493232.5 | n.5152del | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 18, 2019 | 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. This variant has not been reported in the literature in individuals with BRAT1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a frameshift in the BRAT1 gene (p.Asp816Thrfs*65). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acids of the BRAT1 protein and extend the protein by an additional 58 amino acids. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at