rs78339727
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_020964.3(EPG5):c.3248C>T(p.Ser1083Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0294 in 1,596,020 control chromosomes in the GnomAD database, including 880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S1083S) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.021 ( 59 hom., cov: 32)
Exomes 𝑓: 0.030 ( 821 hom. )
Consequence
EPG5
NM_020964.3 missense
NM_020964.3 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 3.89
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 18-45916574-G-A is Benign according to our data. Variant chr18-45916574-G-A is described in ClinVar as [Benign]. Clinvar id is 466245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45916574-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0214 (3256/152170) while in subpopulation SAS AF= 0.0415 (200/4816). AF 95% confidence interval is 0.0368. There are 59 homozygotes in gnomad4. There are 1606 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 59 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPG5 | NM_020964.3 | c.3248C>T | p.Ser1083Leu | missense_variant | 18/44 | ENST00000282041.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPG5 | ENST00000282041.11 | c.3248C>T | p.Ser1083Leu | missense_variant | 18/44 | 1 | NM_020964.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0214 AC: 3258AN: 152052Hom.: 58 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0266 AC: 6592AN: 247554Hom.: 142 AF XY: 0.0285 AC XY: 3820AN XY: 134254
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GnomAD4 exome AF: 0.0302 AC: 43652AN: 1443850Hom.: 821 Cov.: 31 AF XY: 0.0311 AC XY: 22205AN XY: 713888
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GnomAD4 genome ? AF: 0.0214 AC: 3256AN: 152170Hom.: 59 Cov.: 32 AF XY: 0.0216 AC XY: 1606AN XY: 74398
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127
ALSPAC
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105
ESP6500AA
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27
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231
ExAC
?
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3339
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 11, 2018 | - - |
Vici syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;.
Polyphen
D;D
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -31
Find out detailed SpliceAI scores and Pangolin per-transcript scores at