5-865539-T-G

Position:

• chr5-865539-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023924.5(BRD9):​c.1568A>C​(p.Asn523Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRD9 NM_023924.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

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]

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=0.12888345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD9	NM_023924.5	c.1568A>C	p.Asn523Thr	missense_variant	15/16	ENST00000467963.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD9	ENST00000467963.6	c.1568A>C	p.Asn523Thr	missense_variant	15/16	2	NM_023924.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.1568A>C (p.N523T) alteration is located in exon 15 (coding exon 15) of the BRD9 gene. This alteration results from a A to C substitution at nucleotide position 1568, causing the asparagine (N) at amino acid position 523 to be replaced by a threonine (T). 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	0.082
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.83
DEOGEN2	Benign	0.053	.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.11
Sift	Benign	0.097	T;D
Sift4G	Benign	0.11	T;T
Polyphen		0.24	.;B
Vest4		0.41
MutPred		0.14		.;Gain of phosphorylation at N523 (P = 0.0298);
MVP		0.14
MPC		0.36
ClinPred		0.11	T
GERP RS		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.054
gMVP		0.099

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-865654;