5-865423-G-A

Variant summary

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

The NM_023924.5(BRD9):​c.1684C>T​(p.His562Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,581,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

BRD9
NM_023924.5 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.68
Variant links:
Genes affected
BRD9 (HGNC:25818): (bromodomain containing 9) Enables lysine-acetylated histone binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2022]

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
BRD9NM_023924.5 linkc.1684C>T p.His562Tyr missense_variant Exon 15 of 16 ENST00000467963.6 NP_076413.3 Q9H8M2-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRD9ENST00000467963.6 linkc.1684C>T p.His562Tyr missense_variant Exon 15 of 16 2 NM_023924.5 ENSP00000419765.1 Q9H8M2-5

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152260
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000333
AC:
8
AN:
240260
Hom.:
0
AF XY:
0.0000384
AC XY:
5
AN XY:
130242
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000634
Gnomad OTH exome
AF:
0.000173
GnomAD4 exome
AF:
0.0000217
AC:
31
AN:
1429124
Hom.:
0
Cov.:
31
AF XY:
0.0000113
AC XY:
8
AN XY:
706202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000256
Gnomad4 OTH exome
AF:
0.0000509
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000476
Hom.:
0
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1684C>T (p.H562Y) alteration is located in exon 15 (coding exon 15) of the BRD9 gene. This alteration results from a C to T substitution at nucleotide position 1684, causing the histidine (H) at amino acid position 562 to be replaced by a tyrosine (Y). 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
Benign
0.11
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
.;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.43
T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
1.9
.;L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.19
Sift
Benign
0.039
D;T
Sift4G
Uncertain
0.0030
D;T
Polyphen
0.89
.;P
Vest4
0.58
MVP
0.64
MPC
0.59
ClinPred
0.20
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.16
gMVP
0.32

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: rs369221536; hg19: chr5-865538; API