rs1057519509

Variant names:

• chr3-9739507-C-T
• rs1057519509
• NM_001003694.2:c.1108C>T
• BRPF1 p.Pro370Ser

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001003694.2(BRPF1):​c.1108C>T​(p.Pro370Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRPF1 NM_001003694.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.57
• Publications: 3 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: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903
• PP5: Variant 3-9739507-C-T is Pathogenic according to our data. Variant chr3-9739507-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 375484.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1108C>T	p.Pro370Ser	missense	Exon 3 of 14	NP_001003694.1	P55201-2
	BRPF1	NM_001437892.1		c.1108C>T	p.Pro370Ser	missense	Exon 3 of 13	NP_001424821.1	A0A804HI52
	BRPF1	NM_001438342.1		c.1108C>T	p.Pro370Ser	missense	Exon 3 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.1108C>T	p.Pro370Ser	missense	Exon 3 of 14	ENSP00000373340.2	P55201-2
	BRPF1	ENST00000424362.7	TSL:1	c.1108C>T	p.Pro370Ser	missense	Exon 3 of 14	ENSP00000398863.2	A0A8C8KWW5
	BRPF1	ENST00000919141.1		c.1108C>T	p.Pro370Ser	missense	Exon 3 of 13	ENSP00000589200.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Intellectual developmental disorder with dysmorphic facies and ptosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		7.6
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.94
gMVP		0.93
Mutation Taster		=0/100	disease causing (ClinVar)

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

dbSNP: rs1057519509;

hg19: chr3-9781191;