rs797045417

Positions:

chrX-80717699-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_ModerateBP6_ModerateBS1BS2

The NM_153252.5(BRWD3):c.2105G>A(p.Ser702Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,209,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 6 hem. )

Consequence

BRWD3
NM_153252.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.07

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]

BRWD3 links:

BRWD3 (HGNC:):

BRWD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), BRWD3. . Gene score misZ 4.269 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked syndromic intellectual disability, West syndrome, intellectual disability, X-linked 93, childhood epilepsy with centrotemporal spikes.

BP4

Computational evidence support a benign effect (MetaRNN=0.18772128).

BP6

Variant X-80717699-C-T is Benign according to our data. Variant chrX-80717699-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 210538.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000155 (17/1097737) while in subpopulation NFE AF= 0.0000202 (17/841697). AF 95% confidence interval is 0.0000123. There are 0 homozygotes in gnomad4_exome. There are 6 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRWD3	NM_153252.5 linkuse as main transcript	c.2105G>A	p.Ser702Asn	missense_variant	19/41	ENST00000373275.5	NP_694984.5	Q6RI45-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BRWD3	ENST00000373275.5 linkuse as main transcript	c.2105G>A	p.Ser702Asn	missense_variant	19/41	1	NM_153252.5	ENSP00000362372.4	Q6RI45-1
BRWD3	ENST00000473691.1 linkuse as main transcript	n.241G>A		non_coding_transcript_exon_variant	3/25	2
BRWD3	ENST00000497335.1 linkuse as main transcript	n.143G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111997

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34165

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183336

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1097737

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363175

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111997

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34165

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 08, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.49

M_CAP

Benign

0.019

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.2

REVEL

Benign

0.12

Sift

Benign

0.036

Sift4G

Uncertain

0.0030

Polyphen

0.26

Vest4

0.12

MutPred

0.26

Loss of phosphorylation at S702 (P = 0.0106);

MVP

0.65

MPC

0.88

ClinPred

0.23

GERP RS

2.4

Varity_R

0.33

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over