3-9744393-GC-GCCC

Variant names:

• chr3-9744393-G-GCC
• rs762904815
• NM_001003694.2:c.2811_2812dupCC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001003694.2(BRPF1):​c.2811_2812dupCC​(p.Gln938ProfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRPF1 NM_001003694.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 1 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

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• 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.2811_2812dupCC	p.Gln938ProfsTer6	frameshift	Exon 9 of 14	NP_001003694.1
	BRPF1	NM_001437892.1		c.2793_2794dupCC	p.Gln932ProfsTer6	frameshift	Exon 9 of 13	NP_001424821.1
	BRPF1	NM_001438342.1		c.2790_2791dupCC	p.Gln931ProfsTer6	frameshift	Exon 9 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.2811_2812dupCC	p.Gln938ProfsTer6	frameshift	Exon 9 of 14	ENSP00000373340.2
	BRPF1	ENST00000424362.7	TSL:1	c.2808_2809dupCC	p.Gln937ProfsTer6	frameshift	Exon 9 of 14	ENSP00000398863.2
	BRPF1	ENST00000919141.1		c.2811_2812dupCC	p.Gln938ProfsTer6	frameshift	Exon 9 of 13	ENSP00000589200.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000424 AC: 1 AN: 235928 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000105

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762904815; hg19: chr3-9786077;