rs140494095
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_020964.3(EPG5):c.740C>T(p.Pro247Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00193 in 1,614,216 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P247P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0018 ( 51 hom. )
Consequence
EPG5
NM_020964.3 missense
NM_020964.3 missense
Scores
2
7
8
Clinical Significance
Conservation
PhyloP100: 5.89
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0067515373).
BP6
?
Variant 18-45954662-G-A is Benign according to our data. Variant chr18-45954662-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 466264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45954662-G-A is described in Lovd as [Likely_benign]. Variant chr18-45954662-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00281 (428/152332) while in subpopulation AMR AF= 0.0156 (239/15298). AF 95% confidence interval is 0.014. There are 2 homozygotes in gnomad4. There are 245 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPG5 | NM_020964.3 | c.740C>T | p.Pro247Leu | missense_variant | 2/44 | ENST00000282041.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPG5 | ENST00000282041.11 | c.740C>T | p.Pro247Leu | missense_variant | 2/44 | 1 | NM_020964.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00283 AC: 431AN: 152214Hom.: 2 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
431
AN:
152214
Hom.:
Cov.:
33
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: 0.00660 AC: 1646AN: 249442Hom.: 32 AF XY: 0.00521 AC XY: 705AN XY: 135326
GnomAD3 exomes
AF:
AC:
1646
AN:
249442
Hom.:
AF XY:
AC XY:
705
AN XY:
135326
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: 0.00184 AC: 2695AN: 1461884Hom.: 51 Cov.: 32 AF XY: 0.00169 AC XY: 1229AN XY: 727242
GnomAD4 exome
AF:
AC:
2695
AN:
1461884
Hom.:
Cov.:
32
AF XY:
AC XY:
1229
AN XY:
727242
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: 0.00281 AC: 428AN: 152332Hom.: 2 Cov.: 33 AF XY: 0.00329 AC XY: 245AN XY: 74482
GnomAD4 genome
?
AF:
AC:
428
AN:
152332
Hom.:
Cov.:
33
AF XY:
AC XY:
245
AN XY:
74482
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:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
0
ESP6500AA
AF:
AC:
3
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
682
Asia WGS
AF:
AC:
57
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Vici syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 17, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 18, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Pathogenic
D;.
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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