dbSNP rs139052198: BRD3:p.Ala422Ser (chr9-134041903-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007371.4(BRD3):c.1264G>T(p.Ala422Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,607,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

BRD3
NM_007371.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Publications

0 publications found

Variant links:

Genes affected

BRD3 (HGNC:1104): (bromodomain containing 3) This gene was identified based on its homology to the gene encoding the RING3 protein, a serine/threonine kinase. The gene localizes to 9q34, a region which contains several major histocompatibility complex (MHC) genes. The function of the encoded protein is not known. [provided by RefSeq, Jul 2008]

BRD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03670159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD3	NM_007371.4 link	c.1264G>T	p.Ala422Ser	missense_variant	Exon 8 of 12	ENST00000303407.12	NP_031397.1	Q15059-1A0A024R8H6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BRD3	ENST00000303407.12 link	c.1264G>T	p.Ala422Ser	missense_variant	Exon 8 of 12	1	NM_007371.4	ENSP00000305918.6	Q15059-1
BRD3	ENST00000371834.6 link	c.1264G>T	p.Ala422Ser	missense_variant	Exon 8 of 10	1		ENSP00000360900.2	Q15059-2
BRD3	ENST00000473349.1 link	n.-109G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

244220

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.000189

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455274

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723402

show subpopulations

African (AFR)

AF:

0.0000900

AC:

AN:

33334

American (AMR)

AF:

0.00

AC:

AN:

44110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25782

East Asian (EAS)

AF:

0.00

AC:

AN:

39536

South Asian (SAS)

AF:

0.00

AC:

AN:

85786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108418

Other (OTH)

AF:

0.0000166

AC:

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000658

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 16, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1264G>T (p.A422S) alteration is located in exon 8 (coding exon 7) of the BRD3 gene. This alteration results from a G to T substitution at nucleotide position 1264, causing the alanine (A) at amino acid position 422 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.052

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;N

PhyloP100

1.6

PrimateAI

Benign

0.38

PROVEAN

Benign

0.16

N;N

REVEL

Benign

0.043

Sift

Benign

1.0

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.016

B;B

Vest4

0.26

MVP

0.28

MPC

0.68

ClinPred

0.016

GERP RS

4.1

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.020

gMVP

0.33

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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