rs1555905780
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001429.4(EP300):c.272del(p.Pro91LeufsTer25) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S90S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
EP300
NM_001429.4 frameshift
NM_001429.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.56
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 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 22-41117360-TC-T is Pathogenic according to our data. Variant chr22-41117360-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 520753.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.272del | p.Pro91LeufsTer25 | frameshift_variant | 2/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.272del | p.Pro91LeufsTer25 | frameshift_variant | 2/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.272del | p.Pro91LeufsTer25 | frameshift_variant | 2/31 | 1 | NM_001429.4 | P2 | |
EP300 | ENST00000674155.1 | c.272del | p.Pro91LeufsTer25 | frameshift_variant | 2/30 | A2 | |||
EP300 | ENST00000703544.1 | c.272del | p.Pro91LeufsTer25 | frameshift_variant, NMD_transcript_variant | 2/30 | ||||
EP300 | ENST00000703545.1 | c.156del | p.Pro53LeufsTer25 | frameshift_variant, NMD_transcript_variant | 1/17 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2015 | - - |
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