5-878410-T-C

Variant names:

• chr5-878410-T-C
• NM_023924.5:c.1216A>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.1216A>G​(p.Met406Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,395,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 38)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: BRD9 NM_023924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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=0.077693254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD9	NM_023924.5	c.1216A>G	p.Met406Val	missense_variant	Exon 11 of 16	ENST00000467963.6	NP_076413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD9	ENST00000467963.6	c.1216A>G	p.Met406Val	missense_variant	Exon 11 of 16	2	NM_023924.5	ENSP00000419765.1

Frequencies

GnomAD3 genomes Cov.: 38

GnomAD4 exome AF: 0.00000287 AC: 4 AN: 1395520 Hom.: 0 Cov.: 82 AF XY: 0.00000144 AC XY: 1 AN XY: 694888

Gnomad4 AFR exome AF: 0.00

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: 0.00000377

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.4
DANN	Benign	0.63
DEOGEN2	Benign	0.072	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.043
Sift	Benign	0.23	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.35
MutPred		0.23		.;Gain of sheet (P = 0.0477);
MVP		0.28
MPC		0.35
ClinPred		0.060	T
GERP RS		-1.6
Varity_R		0.052
gMVP		0.42

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: chr5-878525;