rs1057518835
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate
The NM_001429.4(EP300):āc.1619A>Gā(p.Gln540Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
EP300
NM_001429.4 missense
NM_001429.4 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 8.46
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.838
BP6
?
Variant 22-41135903-A-G is Benign according to our data. Variant chr22-41135903-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 374013.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.1619A>G | p.Gln540Arg | missense_variant | 7/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.1619A>G | p.Gln540Arg | missense_variant | 7/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.1619A>G | p.Gln540Arg | missense_variant | 7/31 | 1 | NM_001429.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1458840Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 725922
GnomAD4 exome
AF:
AC:
1
AN:
1458840
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
725922
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Micrognathia;C0232466:Feeding difficulties;C0234853:Facial grimacing;C0557874:Global developmental delay;C0575897:Thumb deformity Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Aug 26, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of glycosylation at S539 (P = 0.0786);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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