22-41149144-C-A

Position:

• chr22-41149144-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000263253.9(EP300):​c.2348C>A​(p.Ala783Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A783V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EP300 ENST00000263253.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16

Genes affected

EP300 (HGNC:3373): (E1A binding protein p300) This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.299647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EP300	NM_001429.4	c.2348C>A	p.Ala783Asp	missense_variant	13/31	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.2270C>A	p.Ala757Asp	missense_variant	12/30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.2348C>A	p.Ala783Asp	missense_variant	13/31	1	NM_001429.4	ENSP00000263253	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	0.96	D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.013	D;.
Sift4G	Benign	0.073	T;D
Polyphen		0.98	D;.
Vest4		0.48
MutPred		0.30		Gain of phosphorylation at S786 (P = 0.1946);.;
MVP		0.79
ClinPred		0.69	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.30

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: chr22-41545148;