5-865483-C-A

Position:

• chr5-865483-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_023924.5(BRD9):​c.1624G>T​(p.Gly542Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 6.83

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3620241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD9	NM_023924.5	c.1624G>T	p.Gly542Cys	missense_variant	15/16	ENST00000467963.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD9	ENST00000467963.6	c.1624G>T	p.Gly542Cys	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

Feb 23, 2023

The c.1624G>T (p.G542C) alteration is located in exon 15 (coding exon 15) of the BRD9 gene. This alteration results from a G to T substitution at nucleotide position 1624, causing the glycine (G) at amino acid position 542 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.64	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.96	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.039	D;D
Polyphen		1.0	.;D
Vest4		0.52
MutPred		0.17		.;Gain of helix (P = 0.0425);
MVP		0.40
MPC		1.1
ClinPred		0.81	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.39

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: chr5-865598;