Genetic Variant NM_001003694.2:c.208C>G (chr3-9734348-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001003694.2(BRPF1):c.208C>G(p.Pro70Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

BRPF1
NM_001003694.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.614

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036256194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRPF1	NM_001003694.2 link	c.208C>G	p.Pro70Ala	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 link	c.208C>G	p.Pro70Ala	missense_variant	Exon 2 of 14	1	NM_001003694.2	ENSP00000373340.2		P55201-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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.208C>G (p.P70A) alteration is located in exon 2 (coding exon 1) of the BRPF1 gene. This alteration results from a C to G substitution at nucleotide position 208, causing the proline (P) at amino acid position 70 to be replaced by an alanine (A). 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

0.043

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.024

.;.;.;.;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

T;T;T;D;D;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.036

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N;N;.;.;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.46

N;N;N;N;N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.69

T;T;T;T;T;T

Polyphen

0.0

B;B;B;.;.;B

Vest4

0.14

MutPred

0.16

Loss of glycosylation at P70 (P = 0.0394);Loss of glycosylation at P70 (P = 0.0394);Loss of glycosylation at P70 (P = 0.0394);Loss of glycosylation at P70 (P = 0.0394);Loss of glycosylation at P70 (P = 0.0394);Loss of glycosylation at P70 (P = 0.0394);

MVP

0.31

MPC

0.81

ClinPred

0.058

GERP RS

4.8

Varity_R

0.053

gMVP

0.24

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over