rs1321690570

Variant names:

• chr9-134048349-T-C
• NM_007371.4:c.820A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-134048349-T-C
• chr9-134048349-T-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.820A>G​(p.Lys274Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,446,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. K274Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BRD3 NM_007371.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79

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=0.23516735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD3	NM_007371.4	c.820A>G	p.Lys274Glu	missense_variant	Exon 6 of 12	ENST00000303407.12	NP_031397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD3	ENST00000303407.12	c.820A>G	p.Lys274Glu	missense_variant	Exon 6 of 12	1	NM_007371.4	ENSP00000305918.6
BRD3	ENST00000371834.6	c.820A>G	p.Lys274Glu	missense_variant	Exon 6 of 10	1		ENSP00000360900.2
BRD3	ENST00000494743.1	n.160A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446976 Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1 AN XY: 720196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.0028	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	0.073
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.11
Sift	Uncertain	0.024	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.43	B;B
Vest4		0.39
MutPred		0.28		Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);
MVP		0.57
MPC		2.0
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr9-136913471;