3-9734388-A-T

Variant names:

• chr3-9734388-A-T
• NM_001003694.2:c.248A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003694.2(BRPF1):​c.248A>T​(p.Gln83Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BRPF1 NM_001003694.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.64

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]

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=0.2060507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRPF1	NM_001003694.2	c.248A>T	p.Gln83Leu	missense_variant	Exon 2 of 14	ENST00000383829.7	NP_001003694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRPF1	ENST00000383829.7	c.248A>T	p.Gln83Leu	missense_variant	Exon 2 of 14	1	NM_001003694.2	ENSP00000373340.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.248A>T (p.Q83L) alteration is located in exon 2 (coding exon 1) of the BRPF1 gene. This alteration results from a A to T substitution at nucleotide position 248, causing the glutamine (Q) at amino acid position 83 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	.;.;.;.;.;T
Eigen	Benign	-0.013
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T;T;T;D;D;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;L;.;.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.92	N;N;N;D;N;N
REVEL	Benign	0.16
Sift	Benign	0.67	T;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T
Polyphen		0.63	P;B;B;.;.;B
Vest4		0.44
MutPred		0.30		Loss of solvent accessibility (P = 0.0098);Loss of solvent accessibility (P = 0.0098);Loss of solvent accessibility (P = 0.0098);Loss of solvent accessibility (P = 0.0098);Loss of solvent accessibility (P = 0.0098);Loss of solvent accessibility (P = 0.0098);
MVP		0.43
MPC		1.0
ClinPred		0.83	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.36

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: chr3-9776072;