NM_007371.4:c.1633A>C

Variant names:

• chr9-134040044-T-G
• rs2132392562
• NM_007371.4:c.1633A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007371.4(BRD3):​c.1633A>C​(p.Thr545Pro) 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. T545M) 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: -1.83
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06358731).

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.1633A>C	p.Thr545Pro	missense	Exon 9 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.1633A>C	p.Thr545Pro	missense	Exon 9 of 12	ENSP00000305918.6	Q15059-1
	BRD3	ENST00000371834.6	TSL:1	c.1633A>C	p.Thr545Pro	missense	Exon 9 of 10	ENSP00000360900.2	Q15059-2
	BRD3	ENST00000883998.1		c.1633A>C	p.Thr545Pro	missense	Exon 9 of 12	ENSP00000554057.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.066
DANN	Benign	0.75
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.062
Sift	Benign	0.24	T
Sift4G	Benign	0.35	T
Polyphen		0.015	B
Vest4		0.12
MutPred		0.24		Loss of phosphorylation at T545 (P = 0.0258)
MVP		0.59
MPC		0.95
ClinPred		0.15	T
GERP RS		-9.5
Varity_R		0.064
gMVP		0.17
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2132392562; hg19: chr9-136905166;