rs730882186

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

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.80
Variant links:
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]

Genome browser will be placed here

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
BRWD3NM_153252.5 linkuse as main transcriptc.946_947insA p.Arg316LysfsTer22 frameshift_variant 10/41 ENST00000373275.5 NP_694984.5
BRWD3XM_005262113.4 linkuse as main transcriptc.946_947insA p.Arg316LysfsTer22 frameshift_variant 10/40 XP_005262170.1
BRWD3XM_017029385.3 linkuse as main transcriptc.946_947insA p.Arg316LysfsTer22 frameshift_variant 10/22 XP_016884874.1
BRWD3XM_047441957.1 linkuse as main transcriptc.946_947insA p.Arg316LysfsTer22 frameshift_variant 10/38 XP_047297913.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BRWD3ENST00000373275.5 linkuse as main transcriptc.946_947insA p.Arg316LysfsTer22 frameshift_variant 10/411 NM_153252.5 ENSP00000362372 P1Q6RI45-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
28
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 providedliterature onlyOMIMAug 01, 2007- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs730882186; hg19: chrX-79990664; API