NM_023924.5:c.1610C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023924.5(BRD9):​c.1610C>T​(p.Ala537Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000299 in 1,607,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

BRD9
NM_023924.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09529239).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRD9NM_023924.5 linkc.1610C>T p.Ala537Val 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.1610C>T p.Ala537Val missense_variant Exon 15 of 16 2 NM_023924.5 ENSP00000419765.1 Q9H8M2-5

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000555
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000282
AC:
7
AN:
248228
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134424
show subpopulations
Gnomad AFR exome
AF:
0.000431
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000172
AC:
25
AN:
1455222
Hom.:
0
Cov.:
31
AF XY:
0.00000829
AC XY:
6
AN XY:
723620
show subpopulations
Gnomad4 AFR exome
AF:
0.000628
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.000555
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000664
Hom.:
0
Bravo
AF:
0.000117
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1610C>T (p.A537V) 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 1610, causing the alanine (A) at amino acid position 537 to be replaced by a valine (V). 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
0.095
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.026
.;T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.40
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.85
T;T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.095
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
.;L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
0.0
N;N
REVEL
Benign
0.087
Sift
Benign
0.36
T;T
Sift4G
Benign
0.086
T;T
Polyphen
0.30
.;B
Vest4
0.49
MVP
0.27
MPC
0.40
ClinPred
0.095
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.035
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: rs148724954; hg19: chr5-865612; API