chr5-865483-C-A

Variant names:

• chr5-865483-C-A
• rs767016534
• NM_023924.5:c.1624G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023924.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD9	NM_023924.5	MANE Select	c.1624G>T	p.Gly542Cys	missense	Exon 15 of 16	NP_076413.3	Q9H8M2-5
	BRD9	NM_001375861.1		c.1774G>T	p.Gly592Cys	missense	Exon 16 of 17	NP_001362790.1
	BRD9	NM_001375862.1		c.1747G>T	p.Gly583Cys	missense	Exon 16 of 17	NP_001362791.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD9	ENST00000467963.6	TSL:2 MANE Select	c.1624G>T	p.Gly542Cys	missense	Exon 15 of 16	ENSP00000419765.1	Q9H8M2-5
	BRD9	ENST00000489816.5	TSL:1	n.*1466G>T		non_coding_transcript_exon	Exon 16 of 17	ENSP00000419752.1	F2Z2E8
	BRD9	ENST00000490814.6	TSL:1	n.*2262G>T		non_coding_transcript_exon	Exon 18 of 19	ENSP00000417431.2	F2Z2E8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.17
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.039	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
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs767016534; hg19: chr5-865598; COSMIC: COSV106059965; COSMIC: COSV106059965;