9-134036143-A-C

Variant names:

• chr9-134036143-A-C
• rs1340507235
• NM_007371.4:c.1825T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007371.4(BRD3):​c.1825T>G​(p.Ser609Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRD3 NM_007371.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21270043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD3	NM_007371.4	c.1825T>G	p.Ser609Ala	missense_variant	Exon 10 of 12	ENST00000303407.12	NP_031397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD3	ENST00000303407.12	c.1825T>G	p.Ser609Ala	missense_variant	Exon 10 of 12	1	NM_007371.4	ENSP00000305918.6
BRD3	ENST00000371834	c.*421T>G		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000360900.2
BRD3	ENST00000473349.1	n.217T>G		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1825T>G (p.S609A) alteration is located in exon 10 (coding exon 9) of the BRD3 gene. This alteration results from a T to G substitution at nucleotide position 1825, causing the serine (S) at amino acid position 609 to be replaced by an alanine (A). 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.12
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.027	D
Polyphen		0.23	B
Vest4		0.10
MutPred		0.30		Gain of relative solvent accessibility (P = 0.005);
MVP		0.64
MPC		1.3
ClinPred		0.92	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.26
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs1340507235; hg19: chr9-136901265;