rs747187417
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_001429.4(EP300):c.3750C>G(p.Cys1250Trp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1250Y) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001429.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.3750C>G | p.Cys1250Trp | missense_variant | 22/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.3672C>G | p.Cys1224Trp | missense_variant | 21/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.3750C>G | p.Cys1250Trp | missense_variant | 22/31 | 1 | NM_001429.4 | P2 | |
EP300 | ENST00000674155.1 | c.3672C>G | p.Cys1224Trp | missense_variant | 21/30 | A2 | |||
EP300 | ENST00000635584.1 | n.75C>G | non_coding_transcript_exon_variant | 2/6 | 4 | ||||
EP300 | ENST00000703544.1 | c.*1670C>G | 3_prime_UTR_variant, NMD_transcript_variant | 21/30 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 01, 2017 | Likely pathogenicity based on finding it once in our laboratory de novo in a 2-year-old male with complex CHD, developmental delay, microcephaly, dysmorphisms, unsteady gait, resolved hypocalcaemia - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at