18-45917745-A-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.3173T>C(p.Val1058Ala) variant causes a missense change. The variant allele was found at a frequency of 0.53 in 1,613,394 control chromosomes in the GnomAD database, including 231,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17729 hom., cov: 32)

Exomes 𝑓: 0.54 ( 213706 hom. )

Consequence

EPG5
NM_020964.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 6.65

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=3.9723516E-4).

BP6

Variant 18-45917745-A-G is Benign according to our data. Variant chr18-45917745-A-G is described in ClinVar as [Benign]. Clinvar id is 402833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45917745-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3 link	c.3173T>C	p.Val1058Ala	missense_variant	Exon 17 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.3173T>C	p.Val1058Ala	missense_variant	Exon 17 of 44	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71123

AN:

151958

Hom.:

17724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.738

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.493

GnomAD3 exomes

AF:

0.490

AC:

122181

AN:

249322

Hom.:

31282

AF XY:

0.494

AC XY:

66818

AN XY:

135274

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.339

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.583

Gnomad SAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.494

GnomAD4 exome

AF:

0.536

AC:

783929

AN:

1461318

Hom.:

213706

Cov.:

AF XY:

0.534

AC XY:

388019

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.533

Gnomad4 EAS exome

AF:

0.561

Gnomad4 SAS exome

AF:

0.397

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.562

Gnomad4 OTH exome

AF:

0.524

GnomAD4 genome

AF:

0.468

AC:

71153

AN:

152076

Hom.:

17729

Cov.:

AF XY:

0.466

AC XY:

34610

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.304

Gnomad4 AMR

AF:

0.415

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.582

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.529

Gnomad4 NFE

AF:

0.559

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.540

Hom.:

56933

Bravo

AF:

0.454

TwinsUK

AF:

0.559

AC:

2074

ALSPAC

AF:

0.568

AC:

2188

ESP6500AA

AF:

0.293

AC:

1105

ESP6500EA

AF:

0.565

AC:

4654

ExAC

AF:

0.490

AC:

59268

Asia WGS

AF:

0.444

AC:

1547

AN:

3478

EpiCase

AF:

0.557

EpiControl

AF:

0.550

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Vici syndrome

Benign:3

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2Other:1

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. -

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

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: Frequency -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

.;T

MetaRNN

Benign

0.00040

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.5

N;.

REVEL

Benign

0.094

Sift

Uncertain

0.0040

D;.

Sift4G

Pathogenic

0.0

D;.

Polyphen

0.88

P;P

Vest4

0.23

MPC

0.66

ClinPred

0.027

GERP RS

5.4

Varity_R

0.20

gMVP

0.60

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