rs78339727

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.89

Publications

11 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 -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 VariationId is 466245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3 link	c.3248C>T	p.Ser1083Leu	missense_variant	Exon 18 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.3248C>T	p.Ser1083Leu	missense_variant	Exon 18 of 44	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3258

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00645

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.0415

Gnomad FIN

AF:

0.0363

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.0266

AC:

6592

AN:

247554

AF XY:

0.0285

show subpopulations

Gnomad AFR exome

AF:

0.00525

Gnomad AMR exome

AF:

0.00735

Gnomad ASJ exome

AF:

0.0234

Gnomad EAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.0397

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.0302

AC:

43652

AN:

1443850

Hom.:

821

Cov.:

AF XY:

0.0311

AC XY:

22205

AN XY:

713888

show subpopulations

African (AFR)

AF:

0.00494

AC:

164

AN:

33174

American (AMR)

AF:

0.00735

AC:

326

AN:

44376

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

625

AN:

25980

East Asian (EAS)

AF:

0.00322

AC:

126

AN:

39076

South Asian (SAS)

AF:

0.0487

AC:

4169

AN:

85638

European-Finnish (FIN)

AF:

0.0396

AC:

2108

AN:

53198

Middle Eastern (MID)

AF:

0.0199

AC:

114

AN:

5722

European-Non Finnish (NFE)

AF:

0.0314

AC:

34474

AN:

1097160

Other (OTH)

AF:

0.0260

AC:

1546

AN:

59526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1886

3772

5658

7544

9430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1320

2640

3960

5280

6600

<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:

0.0214

AC:

3256

AN:

152170

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1606

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00643

AC:

267

AN:

41526

American (AMR)

AF:

0.0109

AC:

166

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

AN:

3468

East Asian (EAS)

AF:

0.00252

AC:

AN:

5168

South Asian (SAS)

AF:

0.0415

AC:

200

AN:

4816

European-Finnish (FIN)

AF:

0.0363

AC:

384

AN:

10592

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0307

AC:

2084

AN:

67992

Other (OTH)

AF:

0.0142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

163

327

490

654

817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0270

Hom.:

135

Bravo

AF:

0.0180

TwinsUK

AF:

0.0343

AC:

127

ALSPAC

AF:

0.0272

AC:

105

ESP6500AA

AF:

0.00665

AC:

ESP6500EA

AF:

0.0276

AC:

231

ExAC

AF:

0.0276

AC:

3339

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0305

EpiControl

AF:

0.0281

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Oct 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

0.097

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.80

.;T

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

3.9

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.5

D;.

REVEL

Benign

0.18

Sift

Uncertain

0.019

D;.

Sift4G

Uncertain

0.010

D;.

Polyphen

1.0

D;D

Vest4

0.13

MPC

0.15

ClinPred

0.017

GERP RS

5.8

Varity_R

0.096

gMVP

0.47

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -31

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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