NM_020964.3:c.5591G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020964.3(EPG5):c.5591G>A(p.Ser1864Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00914 in 1,611,596 control chromosomes in the GnomAD database, including 1,157 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1864R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.049 ( 605 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 552 hom. )

Consequence

EPG5
NM_020964.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.279

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

Vici syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P

EPG5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012777448).

BP6

Variant 18-45880151-C-T is Benign according to our data. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45880151-C-T is described in CliVar as Benign. Clinvar id is 466257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3 link	c.5591G>A	p.Ser1864Asn	missense_variant	Exon 32 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.5591G>A	p.Ser1864Asn	missense_variant	Exon 32 of 44	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7430

AN:

152108

Hom.:

602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0296

GnomAD2 exomes

AF:

0.0125

AC:

3072

AN:

244996

AF XY:

0.00930

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.00865

Gnomad ASJ exome

AF:

0.00623

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000419

Gnomad OTH exome

AF:

0.00551

GnomAD4 exome

AF:

0.00500

AC:

7296

AN:

1459370

Hom.:

552

Cov.:

AF XY:

0.00429

AC XY:

3115

AN XY:

725820

show subpopulations

African (AFR)

AF:

0.170

AC:

5687

AN:

33408

American (AMR)

AF:

0.00984

AC:

439

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.00563

AC:

147

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.000163

AC:

AN:

86118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52794

Middle Eastern (MID)

AF:

0.00469

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000256

AC:

284

AN:

1110646

Other (OTH)

AF:

0.0116

AC:

698

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

360

720

1081

1441

1801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0489

AC:

7442

AN:

152226

Hom.:

605

Cov.:

AF XY:

0.0477

AC XY:

3547

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.169

AC:

7009

AN:

41514

American (AMR)

AF:

0.0195

AC:

299

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68016

Other (OTH)

AF:

0.0293

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

317

634

952

1269

1586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00927

Hom.:

141

Bravo

AF:

0.0559

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.154

AC:

578

ESP6500EA

AF:

0.00159

AC:

ExAC

AF:

0.0149

AC:

1800

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 31, 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

- -

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

0.069

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0045

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.42

.;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.76

N;N

PhyloP100

0.28

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.69

N;.

REVEL

Benign

0.064

Sift

Benign

0.61

T;.

Sift4G

Benign

0.067

T;.

Polyphen

0.0010

B;B

Vest4

0.046

MPC

0.15

ClinPred

0.0013

GERP RS

-2.5

Varity_R

0.046

gMVP

0.14

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over