rs1135402728
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPS1_ModeratePM2
The NM_020964.3(EPG5):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,738 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 no classification for the single variant (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
EPG5
NM_020964.3 start_lost
NM_020964.3 start_lost
Scores
4
7
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.47
Publications
0 publications found
Genes affected
EPG5 (HGNC:29331): (ectopic P-granules 5 autophagy tethering factor) This gene encodes a large coiled coil domain-containing protein that functions in autophagy during starvation conditions. Mutations in this gene cause Vici syndrome. [provided by RefSeq, Aug 2015]
EPG5 Gene-Disease associations (from GenCC):
- Vici syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 4 pathogenic variants. Next in-frame start position is after 80 codons. Genomic position: 45955164. Lost 0.031 part of the original CDS.
PS1
Another start lost variant in NM_020964.3 (EPG5) was described as [Likely_pathogenic] in ClinVar as 267452
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.92e-7 AC: 1AN: 1444738Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 717628 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1444738
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
717628
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32848
American (AMR)
AF:
AC:
0
AN:
42306
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25576
East Asian (EAS)
AF:
AC:
0
AN:
38712
South Asian (SAS)
AF:
AC:
0
AN:
83666
European-Finnish (FIN)
AF:
AC:
0
AN:
52094
Middle Eastern (MID)
AF:
AC:
0
AN:
5724
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1104258
Other (OTH)
AF:
AC:
0
AN:
59554
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
PhyloP100
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Pathogenic
D;.
Polyphen
D;D
Vest4
MutPred
Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);
MVP
ClinPred
D
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
Publications
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