rs878853055
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_153252.5(BRWD3):c.3718C>T(p.Arg1240Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
BRWD3
NM_153252.5 stop_gained
NM_153252.5 stop_gained
Scores
3
1
1
Clinical Significance
Conservation
PhyloP100: 7.64
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 12 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-80689977-G-A is Pathogenic according to our data. Variant chrX-80689977-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 235505.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRWD3 | NM_153252.5 | c.3718C>T | p.Arg1240Ter | stop_gained | 32/41 | ENST00000373275.5 | |
BRWD3 | XM_005262113.4 | c.3568C>T | p.Arg1190Ter | stop_gained | 31/40 | ||
BRWD3 | XM_017029384.2 | c.2506C>T | p.Arg836Ter | stop_gained | 21/30 | ||
BRWD3 | XM_047441957.1 | c.3718C>T | p.Arg1240Ter | stop_gained | 32/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRWD3 | ENST00000373275.5 | c.3718C>T | p.Arg1240Ter | stop_gained | 32/41 | 1 | NM_153252.5 | P1 | |
BRWD3 | ENST00000473691.1 | n.1854C>T | non_coding_transcript_exon_variant | 16/25 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 22, 2016 | - - |
Intellectual disability, X-linked 93 Pathogenic:1
Pathogenic, no assertion criteria provided | case-control | Medical Genetic Institute of Henan Province, Henan Provincial People’s Hospital | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
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