chr9-134045359-C-T

Variant summary

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

The NM_007371.4(BRD3):​c.1149G>A​(p.Met383Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,436 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: 0.0000014 ( 0 hom. )

Consequence

BRD3
NM_007371.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98
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.1149G>A p.Met383Ile 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.1149G>A p.Met383Ile missense_variant Exon 7 of 12 1 NM_007371.4 ENSP00000305918.6 Q15059-1
BRD3ENST00000371834.6 linkc.1149G>A p.Met383Ile missense_variant Exon 7 of 10 1 ENSP00000360900.2 Q15059-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461436
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726998
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Premature ovarian failure Uncertain:1
Mar 02, 2020
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;.
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.43
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.40
N;N
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.6
D;D
REVEL
Benign
0.26
Sift
Benign
0.29
T;T
Sift4G
Benign
0.43
T;T
Polyphen
0.042
B;B
Vest4
0.40
MutPred
0.76
Loss of phosphorylation at Y388 (P = 0.1513);Loss of phosphorylation at Y388 (P = 0.1513);
MVP
0.41
MPC
1.7
ClinPred
0.96
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.65
gMVP
0.85

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: rs1830145204; hg19: chr9-136910481; API