9-134053431-G-T

Variant names:

• chr9-134053431-G-T
• rs200385726
• NM_007371.4:c.47C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007371.4(BRD3):​c.47C>A​(p.Pro16Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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)
• Consequence: BRD3 NM_007371.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 2 publications found

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]

ACMG classification

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=0.23425552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD3	NM_007371.4	c.47C>A	p.Pro16Gln	missense_variant	Exon 2 of 12	ENST00000303407.12	NP_031397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD3	ENST00000303407.12	c.47C>A	p.Pro16Gln	missense_variant	Exon 2 of 12	1	NM_007371.4	ENSP00000305918.6
BRD3	ENST00000371834.6	c.47C>A	p.Pro16Gln	missense_variant	Exon 2 of 10	1		ENSP00000360900.2
BRD3	ENST00000371842.2	c.47C>A	p.Pro16Gln	missense_variant	Exon 2 of 3	5		ENSP00000360908.2
BRD3	ENST00000433041.1	c.47C>A	p.Pro16Gln	missense_variant	Exon 2 of 2	3		ENSP00000406749.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243664 AF XY: 0.00000751

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: 0.00000913

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.059	T;.;T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.037
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T;T;T;.
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.;.
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.95	N;N;N;D
REVEL	Benign	0.12
Sift	Benign	0.61	T;T;T;.
Sift4G	Benign	0.74	T;T;.;.
Polyphen		0.0010	B;D;.;.
Vest4		0.087
MutPred		0.18		Loss of glycosylation at P16 (P = 0.0693);Loss of glycosylation at P16 (P = 0.0693);Loss of glycosylation at P16 (P = 0.0693);Loss of glycosylation at P16 (P = 0.0693);
MVP		0.51
MPC		0.68
ClinPred		0.22	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.40
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs200385726; hg19: chr9-136918553; COSMIC: COSV100325437; COSMIC: COSV100325437;