NM_001003694.2:c.34C>T

Variant names:

• chr3-9734174-C-T
• rs2076900552
• NM_001003694.2:c.34C>T

Variant summary

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

The NM_001003694.2(BRPF1):​c.34C>T​(p.His12Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BRPF1 NM_001003694.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14
• Publications: 0 publications found

Genes affected

BRPF1 (HGNC:14255): (bromodomain and PHD finger containing 1) This gene encodes a bromodomain, PHD finger and chromo/Tudor-related Pro-Trp-Trp-Pro (PWWP) domain containing protein. The encoded protein is a component of the MOZ/MORF histone acetyltransferase complexes which function as a transcriptional regulators. This protein binds to the catalytic MYST domains of the MOZ and MORF proteins and may play a role in stimulating acetyltransferase and transcriptional activity of the complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

BRPF1 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with dysmorphic facies and ptosis

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003694.2. 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
	BRPF1	NM_001003694.2	MANE Select	c.34C>T	p.His12Tyr	missense	Exon 2 of 14	NP_001003694.1	P55201-2
	BRPF1	NM_001437892.1		c.34C>T	p.His12Tyr	missense	Exon 2 of 13	NP_001424821.1	A0A804HI52
	BRPF1	NM_001438342.1		c.34C>T	p.His12Tyr	missense	Exon 2 of 13	NP_001425271.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRPF1	ENST00000383829.7	TSL:1 MANE Select	c.34C>T	p.His12Tyr	missense	Exon 2 of 14	ENSP00000373340.2	P55201-2
	BRPF1	ENST00000424362.7	TSL:1	c.34C>T	p.His12Tyr	missense	Exon 2 of 14	ENSP00000398863.2	A0A8C8KWW5
	BRPF1	ENST00000919141.1		c.34C>T	p.His12Tyr	missense	Exon 2 of 13	ENSP00000589200.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.1
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.23
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.041	D
Polyphen		0.95	P
Vest4		0.60
MutPred		0.39		Gain of sheet (P = 0.0149)
MVP		0.58
MPC		2.1
ClinPred		0.85	D
GERP RS		5.6
PromoterAI		0.0035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.32
gMVP		0.61
Mutation Taster		=42/58	disease causing

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: rs2076900552; hg19: chr3-9775858;