10-32291231-G-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001272004.3(EPC1):āc.907C>Gā(p.Pro303Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 32)
Exomes š: 0.000068 ( 0 hom. )
Consequence
EPC1
NM_001272004.3 missense
NM_001272004.3 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 7.64
Genes affected
EPC1 (HGNC:19876): (enhancer of polycomb homolog 1) This gene encodes a member of the polycomb group (PcG) family. The encoded protein is a component of the NuA4 histone acetyltransferase complex and can act as both a transcriptional activator and repressor. The encoded protein has been linked to apoptosis, DNA repair, skeletal muscle differentiation, gene silencing, and adult T-cell leukemia/lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EPC1 | NM_001272004.3 | c.907C>G | p.Pro303Ala | missense_variant | 6/14 | ENST00000319778.11 | NP_001258933.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EPC1 | ENST00000319778.11 | c.907C>G | p.Pro303Ala | missense_variant | 6/14 | 1 | NM_001272004.3 | ENSP00000318559.6 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152054Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
12
AN:
152054
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000994 AC: 25AN: 251422Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135894
GnomAD3 exomes
AF:
AC:
25
AN:
251422
Hom.:
AF XY:
AC XY:
15
AN XY:
135894
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000684 AC: 100AN: 1461518Hom.: 0 Cov.: 30 AF XY: 0.0000729 AC XY: 53AN XY: 727098
GnomAD4 exome
AF:
AC:
100
AN:
1461518
Hom.:
Cov.:
30
AF XY:
AC XY:
53
AN XY:
727098
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74402
GnomAD4 genome
AF:
AC:
12
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74402
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
9
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2023 | The c.907C>G (p.P303A) alteration is located in exon 6 (coding exon 6) of the EPC1 gene. This alteration results from a C to G substitution at nucleotide position 907, causing the proline (P) at amino acid position 303 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
P;D;D
Vest4
MutPred
Loss of disorder (P = 0.08);.;Loss of disorder (P = 0.08);
MVP
MPC
0.45
ClinPred
T
GERP RS
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