chr5-878410-T-G

Variant names:

• chr5-878410-T-G
• NM_023924.5:c.1216A>C
• BRD9 p.Met406Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023924.5(BRD9):​c.1216A>C​(p.Met406Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M406V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 38)
• Consequence: BRD9 NM_023924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08682293).

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.1216A>C	p.Met406Leu	missense	Exon 11 of 16	NP_076413.3	Q9H8M2-5
	BRD9	NM_001375861.1		c.1366A>C	p.Met456Leu	missense	Exon 12 of 17	NP_001362790.1
	BRD9	NM_001375862.1		c.1339A>C	p.Met447Leu	missense	Exon 12 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.1216A>C	p.Met406Leu	missense	Exon 11 of 16	ENSP00000419765.1	Q9H8M2-5
	BRD9	ENST00000475706.5	TSL:1	n.250A>C		non_coding_transcript_exon	Exon 3 of 6
	BRD9	ENST00000489816.5	TSL:1	n.*908A>C		non_coding_transcript_exon	Exon 11 of 17	ENSP00000419752.1	F2Z2E8

Frequencies

GnomAD3 genomes Cov.: 38

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.70
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.061
Sift	Benign	0.087	T
Sift4G	Benign	0.40	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.089
gMVP		0.45
Mutation Taster		=97/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-878525;