rs779094763

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_153252.5(BRWD3):c.1300T>C(p.Tyr434His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,204,266 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y434N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000028 ( 0 hom. 9 hem. )

Consequence

BRWD3
NM_153252.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.41

Publications

0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13376951).

BP6

Variant X-80728838-A-G is Benign according to our data. Variant chrX-80728838-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 434543.

BS2

High AC in GnomAdExome4 at 31 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153252.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRWD3	NM_153252.5	MANE Select	c.1300T>C	p.Tyr434His	missense	Exon 14 of 41	NP_694984.5
	BRWD3	NM_001441339.1		c.1300T>C	p.Tyr434His	missense	Exon 14 of 40	NP_001428268.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRWD3	ENST00000373275.5	TSL:1 MANE Select	c.1300T>C	p.Tyr434His	missense	Exon 14 of 41	ENSP00000362372.4	Q6RI45-1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111941

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.000663

GnomAD2 exomes

AF:

0.0000219

AC:

AN:

183046

AF XY:

0.0000444

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:

0.0000490

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000284

AC:

AN:

1092273

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

358089

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26294

American (AMR)

AF:

0.00

AC:

AN:

35185

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19330

East Asian (EAS)

AF:

0.00

AC:

AN:

30136

South Asian (SAS)

AF:

0.00

AC:

AN:

53950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40526

Middle Eastern (MID)

AF:

0.000728

AC:

AN:

4123

European-Non Finnish (NFE)

AF:

0.0000323

AC:

AN:

836832

Other (OTH)

AF:

0.0000218

AC:

AN:

45897

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

111993

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34213

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30957

American (AMR)

AF:

0.00

AC:

AN:

10522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3592

South Asian (SAS)

AF:

0.00

AC:

AN:

2730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53010

Other (OTH)

AF:

0.000655

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.090

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.64

M_CAP

Benign

0.0045

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.29

PhyloP100

1.4

PrimateAI

Uncertain

0.65

PROVEAN

Benign

2.0

REVEL

Benign

0.13

Sift

Benign

0.74

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.39

MutPred

0.51

Loss of stability (P = 0.0212)

MVP

0.64

MPC

1.2

ClinPred

0.066

GERP RS

4.7

Varity_R

0.19

gMVP

0.68

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over