9-134045303-C-T

Variant summary

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

The NM_007371.4(BRD3):​c.1205G>A​(p.Arg402Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,038 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: 0.0000021 ( 0 hom. )

Consequence

BRD3
NM_007371.4 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRD3NM_007371.4 linkc.1205G>A p.Arg402Gln missense_variant Exon 7 of 12 ENST00000303407.12 NP_031397.1 Q15059-1A0A024R8H6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRD3ENST00000303407.12 linkc.1205G>A p.Arg402Gln missense_variant Exon 7 of 12 1 NM_007371.4 ENSP00000305918.6 Q15059-1
BRD3ENST00000371834.6 linkc.1205G>A p.Arg402Gln missense_variant Exon 7 of 10 1 ENSP00000360900.2 Q15059-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250742
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135812
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461038
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726826
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1205G>A (p.R402Q) alteration is located in exon 7 (coding exon 6) of the BRD3 gene. This alteration results from a G to A substitution at nucleotide position 1205, causing the arginine (R) at amino acid position 402 to be replaced by a glutamine (Q). 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
0.87
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
T;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.88
L;L
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.7
D;D
REVEL
Benign
0.18
Sift
Uncertain
0.025
D;D
Sift4G
Uncertain
0.043
D;D
Polyphen
0.99
D;D
Vest4
0.57
MutPred
0.52
Loss of MoRF binding (P = 0.0457);Loss of MoRF binding (P = 0.0457);
MVP
0.46
MPC
1.9
ClinPred
0.99
D
GERP RS
4.7
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.1
Varity_R
0.85
gMVP
0.76

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1263501861; hg19: chr9-136910425; API