Genetic Variant NM_007371.4:c.47C>G (chr9-134053431-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007371.4(BRD3):c.47C>G(p.Pro16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P16L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BRD3
NM_007371.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24665171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD3	NM_007371.4 link	c.47C>G	p.Pro16Arg	missense_variant	Exon 2 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.47C>G	p.Pro16Arg	missense_variant	Exon 2 of 12	1	NM_007371.4	ENSP00000305918.6	Q15059-1
BRD3	ENST00000371834.6 link	c.47C>G	p.Pro16Arg	missense_variant	Exon 2 of 10	1		ENSP00000360900.2	Q15059-2
BRD3	ENST00000371842.2 link	c.47C>G	p.Pro16Arg	missense_variant	Exon 2 of 3	5		ENSP00000360908.2	A9J571
BRD3	ENST00000433041.1 link	c.47C>G	p.Pro16Arg	missense_variant	Exon 2 of 2	3		ENSP00000406749.1	A9J575

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458544

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725544

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111532

Other (OTH)

AF:

0.00

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.12

T;.;T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

T;T;T;.

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;M;.;.

PhyloP100

1.3

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.61

N;N;N;D

REVEL

Benign

0.091

Sift

Uncertain

0.027

D;D;D;.

Sift4G

Benign

0.14

T;D;.;.

Polyphen

0.18

B;D;.;.

Vest4

0.15

MutPred

0.27

Gain of methylation at P16 (P = 0.0169);Gain of methylation at P16 (P = 0.0169);Gain of methylation at P16 (P = 0.0169);Gain of methylation at P16 (P = 0.0169);

MVP

0.47

MPC

0.78

ClinPred

0.40

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.048

gMVP

0.49

Mutation Taster

=65/35

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over