rs730882186
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000373275.5(BRWD3):c.946_947insA(p.Arg316LysfsTer22) 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
BRWD3
ENST00000373275.5 frameshift
ENST00000373275.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.80
Genes affected
BRWD3 (HGNC:17342): (bromodomain and WD repeat domain containing 3) The protein encoded by this gene contains a bromodomain and several WD repeats. It is thought to have a chromatin-modifying function, and may thus play a role in transcription. Mutations in this gene are associated with a spectrum of cognitive disabilities and X-linked macrocephaly. This gene is also associated with translocations in patients with B-cell chronic lymphocytic leukemia. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-80735165-C-CT is Pathogenic according to our data. Variant chrX-80735165-C-CT is described in ClinVar as [Pathogenic]. Clinvar id is 10803.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRWD3 | NM_153252.5 | c.946_947insA | p.Arg316LysfsTer22 | frameshift_variant | 10/41 | ENST00000373275.5 | NP_694984.5 | |
BRWD3 | XM_005262113.4 | c.946_947insA | p.Arg316LysfsTer22 | frameshift_variant | 10/40 | XP_005262170.1 | ||
BRWD3 | XM_017029385.3 | c.946_947insA | p.Arg316LysfsTer22 | frameshift_variant | 10/22 | XP_016884874.1 | ||
BRWD3 | XM_047441957.1 | c.946_947insA | p.Arg316LysfsTer22 | frameshift_variant | 10/38 | XP_047297913.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRWD3 | ENST00000373275.5 | c.946_947insA | p.Arg316LysfsTer22 | frameshift_variant | 10/41 | 1 | NM_153252.5 | ENSP00000362372 | P1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual disability, X-linked 93 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2007 | - - |
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