NM_153252.5:c.2105G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

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. 14/21 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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability, X-linked 93
Inheritance: XL, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
X-linked syndromic intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
infantile spasms
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
self-limited epilepsy with centrotemporal spikes
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BRWD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

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 VariationId is 210538.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 17 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRWD3	NM_153252.5 link	c.2105G>A	p.Ser702Asn	missense_variant	Exon 19 of 41	ENST00000373275.5	NP_694984.5	Q6RI45-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BRWD3	ENST00000373275.5 link	c.2105G>A	p.Ser702Asn	missense_variant	Exon 19 of 41	1	NM_153252.5	ENSP00000362372.4	Q6RI45-1
BRWD3	ENST00000473691.1 link	n.241G>A		non_coding_transcript_exon_variant	Exon 3 of 25	2
BRWD3	ENST00000497335.1 link	n.143G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111997

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00000545

AC:

AN:

183336

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

26393

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19373

East Asian (EAS)

AF:

0.00

AC:

AN:

30196

South Asian (SAS)

AF:

0.00

AC:

AN:

54134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000202

AC:

AN:

841697

Other (OTH)

AF:

0.00

AC:

AN:

46081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111997

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34165

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000324

AC:

AN:

30856

American (AMR)

AF:

0.00

AC:

AN:

10501

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3565

South Asian (SAS)

AF:

0.00

AC:

AN:

2731

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6093

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53169

Other (OTH)

AF:

0.00

AC:

AN:

1507

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jan 08, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

3.1

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

Mutation Taster

=73/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over