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GeneBe

22-41125886-A-T

Variant summary

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

The NM_001429.4(EP300):c.752A>T(p.Asn251Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. N251S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

EP300
NM_001429.4 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EP300NM_001429.4 linkuse as main transcriptc.752A>T p.Asn251Ile missense_variant 3/31 ENST00000263253.9
EP300NM_001362843.2 linkuse as main transcriptc.752A>T p.Asn251Ile missense_variant 3/30

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EP300ENST00000263253.9 linkuse as main transcriptc.752A>T p.Asn251Ile missense_variant 3/311 NM_001429.4 P2

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
0.16
BayesDel_addAF
Uncertain
0.024
T
BayesDel_noAF
Benign
-0.20
Cadd
Benign
17
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.72
D
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.87
D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.50
T
MetaSVM
Benign
-0.38
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
0.76
N
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.5
N
REVEL
Uncertain
0.29
Sift
Uncertain
0.011
D
Sift4G
Benign
0.088
T
Polyphen
0.94
P
Vest4
0.53
MutPred
0.19
Loss of glycosylation at P250 (P = 0.0384);
MVP
0.88
ClinPred
0.54
D
GERP RS
1.2
Varity_R
0.11
gMVP
0.37

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: chr22-41521890; API