chr6-36201427-A-T

Variant names:

• chr6-36201427-A-T
• NM_015695.3:c.1105A>T

Variant summary

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

The NM_015695.3(BRPF3):​c.1105A>T​(p.Ser369Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BRPF3 NM_015695.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

Genes affected

BRPF3 (HGNC:14256): (bromodomain and PHD finger containing 3) Predicted to enable histone binding activity. Involved in histone H3-K14 acetylation and positive regulation of DNA replication. Part of MOZ/MORF histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2562167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRPF3	NM_015695.3	c.1105A>T	p.Ser369Cys	missense_variant	Exon 2 of 13	ENST00000357641.10	NP_056510.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRPF3	ENST00000357641.10	c.1105A>T	p.Ser369Cys	missense_variant	Exon 2 of 13	1	NM_015695.3	ENSP00000350267.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1105A>T (p.S369C) alteration is located in exon 2 (coding exon 1) of the BRPF3 gene. This alteration results from a A to T substitution at nucleotide position 1105, causing the serine (S) at amino acid position 369 to be replaced by a cysteine (C). 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	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T;.;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.33
MutPred		0.48		Loss of catalytic residue at M365 (P = 0.0416);Loss of catalytic residue at M365 (P = 0.0416);Loss of catalytic residue at M365 (P = 0.0416);Loss of catalytic residue at M365 (P = 0.0416);
MVP		0.36
MPC		1.4
ClinPred		0.90	D
GERP RS		5.6
Varity_R		0.22
gMVP		0.70

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: chr6-36169204;