rs1555912182
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001429.4(EP300):c.5723dup(p.Thr1909AsnfsTer164) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
EP300
NM_001429.4 frameshift
NM_001429.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.89
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 23 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.5723dup | p.Thr1909AsnfsTer164 | frameshift_variant | 31/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.5645dup | p.Thr1883AsnfsTer164 | frameshift_variant | 30/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.5723dup | p.Thr1909AsnfsTer164 | frameshift_variant | 31/31 | 1 | NM_001429.4 | P2 | |
ENST00000415054.1 | n.82+5630_82+5631insG | intron_variant, non_coding_transcript_variant | 3 | ||||||
EP300-AS1 | ENST00000420537.1 | n.224-2609_224-2608insG | intron_variant, non_coding_transcript_variant | 3 | |||||
EP300 | ENST00000674155.1 | c.5645dup | p.Thr1883AsnfsTer164 | frameshift_variant | 30/30 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Other:1
not provided, no classification provided | literature only | Costain lab, The Hospital for Sick Children | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at