NM_020964.3:c.544A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020964.3(EPG5):c.544A>G(p.Lys182Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,614,110 control chromosomes in the GnomAD database, including 7,085 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1362 hom., cov: 33)

Exomes 𝑓: 0.083 ( 5723 hom. )

Consequence

EPG5
NM_020964.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.10

Variant links:

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 links:

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=0.0038298368).

BP6

Variant 18-45954858-T-C is Benign according to our data. Variant chr18-45954858-T-C is described in ClinVar as [Benign]. Clinvar id is 402834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45954858-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3 link	c.544A>G	p.Lys182Glu	missense_variant	Exon 2 of 44	ENST00000282041.11	NP_066015.2	Q9HCE0-1Q9BTI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000282041.11 link	c.544A>G	p.Lys182Glu	missense_variant	Exon 2 of 44	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17605

AN:

152180

Hom.:

1358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0778

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.0239

Gnomad SAS

AF:

0.0766

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0835

Gnomad OTH

AF:

0.0989

GnomAD3 exomes

AF:

0.0845

AC:

21063

AN:

249294

Hom.:

1105

AF XY:

0.0833

AC XY:

11274

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.0778

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.0233

Gnomad SAS exome

AF:

0.0871

Gnomad FIN exome

AF:

0.0490

Gnomad NFE exome

AF:

0.0802

Gnomad OTH exome

AF:

0.0848

GnomAD4 exome

AF:

0.0826

AC:

120703

AN:

1461812

Hom.:

5723

Cov.:

AF XY:

0.0825

AC XY:

59982

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.219

Gnomad4 AMR exome

AF:

0.0780

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.0207

Gnomad4 SAS exome

AF:

0.0859

Gnomad4 FIN exome

AF:

0.0487

Gnomad4 NFE exome

AF:

0.0809

Gnomad4 OTH exome

AF:

0.0874

GnomAD4 genome

AF:

0.116

AC:

17618

AN:

152298

Hom.:

1362

Cov.:

AF XY:

0.112

AC XY:

8319

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.0777

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.0236

Gnomad4 SAS

AF:

0.0766

Gnomad4 FIN

AF:

0.0439

Gnomad4 NFE

AF:

0.0835

Gnomad4 OTH

AF:

0.0974

Alfa

AF:

0.0897

Hom.:

1170

Bravo

AF:

0.123

TwinsUK

AF:

0.0736

AC:

273

ALSPAC

AF:

0.0734

AC:

283

ESP6500AA

AF:

0.203

AC:

784

ESP6500EA

AF:

0.0832

AC:

687

ExAC

AF:

0.0872

AC:

10530

Asia WGS

AF:

0.0610

AC:

210

AN:

3478

EpiCase

AF:

0.0840

EpiControl

AF:

0.0848

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Vici syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.5

DANN

Benign

0.92

DEOGEN2

Benign

0.0035

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.37

.;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.20

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.24

N;.

REVEL

Benign

0.039

Sift

Benign

0.51

T;.

Sift4G

Benign

0.54

T;.

Polyphen

0.0010

B;B

Vest4

0.065

MPC

0.21

ClinPred

0.0032

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over