rs587778258

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001429.4(EP300):​c.6413C>G​(p.Ala2138Gly) 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. 15/20 in silico tools predict a benign 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

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.573
Variant links:
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)

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ACMG classification

Classification made for transcript

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=0.10664946).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EP300NM_001429.4 linkuse as main transcriptc.6413C>G p.Ala2138Gly missense_variant 31/31 ENST00000263253.9 NP_001420.2
EP300NM_001362843.2 linkuse as main transcriptc.6335C>G p.Ala2112Gly missense_variant 30/30 NP_001349772.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EP300ENST00000263253.9 linkuse as main transcriptc.6413C>G p.Ala2138Gly missense_variant 31/311 NM_001429.4 ENSP00000263253 P2
ENST00000415054.1 linkuse as main transcriptn.82+4939G>C intron_variant, non_coding_transcript_variant 3
EP300-AS1ENST00000420537.1 linkuse as main transcriptn.224-3300G>C intron_variant, non_coding_transcript_variant 3
EP300ENST00000674155.1 linkuse as main transcriptc.6335C>G p.Ala2112Gly missense_variant 30/30 ENSP00000501078 A2

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
Benign
0.096
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
17
DANN
Benign
0.83
DEOGEN2
Benign
0.39
T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.16
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.41
T
MutationAssessor
Benign
-0.035
N
MutationTaster
Benign
0.65
D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.19
N
REVEL
Benign
0.16
Sift
Benign
0.10
T
Sift4G
Benign
0.58
T
Polyphen
0.0010
B
Vest4
0.21
MutPred
0.23
Gain of helix (P = 0.132);
MVP
0.72
ClinPred
0.17
T
GERP RS
4.9
Varity_R
0.092
gMVP
0.39

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: chr22-41574128; API