rs200385726

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-134053431-G-A
• chr9-134053431-G-C
• chr9-134053431-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_007371.4(BRD3):​c.47C>T​(p.Pro16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,610,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: BRD3 NM_007371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24179557).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD3	NM_007371.4	c.47C>T	p.Pro16Leu	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>T	p.Pro16Leu	missense_variant	Exon 2 of 12	1	NM_007371.4	ENSP00000305918.6
BRD3	ENST00000371834.6	c.47C>T	p.Pro16Leu	missense_variant	Exon 2 of 10	1		ENSP00000360900.2
BRD3	ENST00000371842.2	c.47C>T	p.Pro16Leu	missense_variant	Exon 2 of 3	5		ENSP00000360908.2
BRD3	ENST00000433041.1	c.47C>T	p.Pro16Leu	missense_variant	Exon 2 of 2	3		ENSP00000406749.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

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: 0.00000821 AC: 2 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: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000960 AC: 14 AN: 1458544 Hom.: 0 Cov.: 37 AF XY: 0.0000124 AC XY: 9 AN XY: 725544

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111532

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74478

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47C>T (p.P16L) alteration is located in exon 2 (coding exon 1) of the BRD3 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the proline (P) at amino acid position 16 to be replaced by a leucine (L). 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	0.080
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Benign	0.88
DEOGEN2	Benign	0.086	T;.;T;.
Eigen	Benign	0.034
Eigen_PC	Benign	0.065
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T;T;D;.
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M;M;.;.
PhyloP100		1.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.83	N;N;N;D
REVEL	Benign	0.089
Sift	Benign	0.052	T;T;D;.
Sift4G	Benign	0.13	T;T;.;.
Polyphen		0.0040	B;D;.;.
Vest4		0.14
MutPred		0.26		Gain of catalytic residue at P16 (P = 0.053);Gain of catalytic residue at P16 (P = 0.053);Gain of catalytic residue at P16 (P = 0.053);Gain of catalytic residue at P16 (P = 0.053);
MVP		0.47
MPC		0.75
ClinPred		0.32	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.045
gMVP		0.41
Mutation Taster		=67/33	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;