rs1554293869
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_152743.4(BRAT1):c.1543_1564delinsTC(p.Glu515SerfsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
BRAT1
NM_152743.4 frameshift
NM_152743.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.36
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 7-2539577-CGAGGGCGGAGTCCCTCACCTC-GA is Pathogenic according to our data. Variant chr7-2539577-CGAGGGCGGAGTCCCTCACCTC-GA is described in ClinVar as [Pathogenic]. Clinvar id is 540176.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAT1 | NM_152743.4 | c.1543_1564delinsTC | p.Glu515SerfsTer15 | frameshift_variant | 12/14 | ENST00000340611.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAT1 | ENST00000340611.9 | c.1543_1564delinsTC | p.Glu515SerfsTer15 | frameshift_variant | 12/14 | 1 | NM_152743.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neonatal-onset encephalopathy with rigidity and seizures Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2018 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRAT1 are known to be pathogenic (PMID: 22279524, 25500575). This variant has not been reported in the literature in individuals with BRAT1-related disease. ClinVar contains an entry for this variant (Variation ID: 540176). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu515Serfs*4) in the BRAT1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at