NM_001429.4:c.6196C>A

Variant names:

• chr22-41177907-C-A
• rs1555912238
• NM_001429.4:c.6196C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001429.4(EP300):​c.6196C>A​(p.Gln2066Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EP300 NM_001429.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82
• Publications: 0 publications found

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]

EP300-AS1 (HGNC:50504): (EP300 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EP300	NM_001429.4	c.6196C>A	p.Gln2066Lys	missense_variant	Exon 31 of 31	ENST00000263253.9	NP_001420.2
EP300	NM_001362843.2	c.6118C>A	p.Gln2040Lys	missense_variant	Exon 30 of 30		NP_001349772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EP300	ENST00000263253.9	c.6196C>A	p.Gln2066Lys	missense_variant	Exon 31 of 31	1	NM_001429.4	ENSP00000263253.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.89	D
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.66
MutPred		0.71		Gain of methylation at Q2066 (P = 0.0173);
MVP		0.87
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.82
gMVP		0.77
Mutation Taster		=30/70	disease causing

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

Other links and lift over

dbSNP: rs1555912238; hg19: chr22-41573911;