chr22-41178373-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM5BP4
The NM_001429.4(EP300):c.6662C>T(p.Pro2221Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,461,876 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2221Q) has been classified as Pathogenic.
Frequency
Consequence
NM_001429.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EP300 | NM_001429.4 | c.6662C>T | p.Pro2221Leu | missense_variant | 31/31 | ENST00000263253.9 | |
EP300 | NM_001362843.2 | c.6584C>T | p.Pro2195Leu | missense_variant | 30/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EP300 | ENST00000263253.9 | c.6662C>T | p.Pro2221Leu | missense_variant | 31/31 | 1 | NM_001429.4 | P2 | |
ENST00000415054.1 | n.82+4690G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
EP300-AS1 | ENST00000420537.1 | n.224-3549G>A | intron_variant, non_coding_transcript_variant | 3 | |||||
EP300 | ENST00000674155.1 | c.6584C>T | p.Pro2195Leu | missense_variant | 30/30 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251286Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.0000481 AC XY: 35AN XY: 727242
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
EP300-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 05, 2023 | The EP300 c.6662C>T variant is predicted to result in the amino acid substitution p.Pro2221Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-41574377-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at