9-134040044-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_007371.4(BRD3):​c.1633A>G​(p.Thr545Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRD3 NM_007371.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042038113).
• BP6: Variant 9-134040044-T-C is Benign according to our data. Variant chr9-134040044-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2337979.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD3	NM_007371.4	c.1633A>G	p.Thr545Ala	missense_variant	Exon 9 of 12	ENST00000303407.12	NP_031397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD3	ENST00000303407.12	c.1633A>G	p.Thr545Ala	missense_variant	Exon 9 of 12	1	NM_007371.4	ENSP00000305918.6
BRD3	ENST00000371834.6	c.1633A>G	p.Thr545Ala	missense_variant	Exon 9 of 10	1		ENSP00000360900.2
BRD3	ENST00000473349.1	n.35+1716A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 21, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.022
DANN	Benign	0.39
DEOGEN2	Benign	0.056	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.17	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.41	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.19	N;N
REVEL	Benign	0.043
Sift	Benign	1.0	T;T
Sift4G	Benign	0.82	T;T
Polyphen		0.015	B;B
Vest4		0.14
MutPred		0.21		Loss of phosphorylation at T545 (P = 0.0258);Loss of phosphorylation at T545 (P = 0.0258);
MVP		0.72
MPC		0.72
ClinPred		0.042	T
GERP RS		-9.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-136905166;