rs1830145204

Variant names:

• chr9-134045359-C-T
• rs1830145204
• NM_007371.4:c.1149G>A

Variant summary

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

The NM_007371.4(BRD3):​c.1149G>A​(p.Met383Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BRD3 NM_007371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007371.4. 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
	BRD3	NM_007371.4	MANE Select	c.1149G>A	p.Met383Ile	missense	Exon 7 of 12	NP_031397.1	Q15059-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD3	ENST00000303407.12	TSL:1 MANE Select	c.1149G>A	p.Met383Ile	missense	Exon 7 of 12	ENSP00000305918.6	Q15059-1
	BRD3	ENST00000371834.6	TSL:1	c.1149G>A	p.Met383Ile	missense	Exon 7 of 10	ENSP00000360900.2	Q15059-2
	BRD3	ENST00000883998.1		c.1149G>A	p.Met383Ile	missense	Exon 7 of 12	ENSP00000554057.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461436 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726998

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Premature ovarian failure (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.40	N
PhyloP100		4.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.26
Sift	Benign	0.29	T
Sift4G	Benign	0.43	T
Polyphen		0.042	B
Vest4		0.40
MutPred		0.76		Loss of phosphorylation at Y388 (P = 0.1513)
MVP		0.41
MPC		1.7
ClinPred		0.96	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.85
Mutation Taster		=38/62	disease causing

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: rs1830145204; hg19: chr9-136910481;