rs377368037
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001429.4(EP300):āc.1150T>Gā(p.Ser384Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000539 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S384S) has been classified as Benign.
Frequency
Consequence
NM_001429.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.1150T>G | p.Ser384Ala | missense_variant | 4/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.1150T>G | p.Ser384Ala | missense_variant | 4/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.1150T>G | p.Ser384Ala | missense_variant | 4/31 | 1 | NM_001429.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000479 AC: 12AN: 250560Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135514
GnomAD4 exome AF: 0.0000581 AC: 85AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.0000633 AC XY: 46AN XY: 727234
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74390
ClinVar
Submissions by phenotype
EP300-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 20, 2023 | The EP300 c.1150T>G variant is predicted to result in the amino acid substitution p.Ser384Ala. To our knowledge, this variant has not been reported in the literature in association with EP300-related disease. Of note, this variant was reported in healthy individuals per a genome sequencing study (Supplementary Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.0094% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant has conflicting interpretations of benign and uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/134063/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Rubinstein-Taybi syndrome due to EP300 haploinsufficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 22, 2023 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at