Variant 18-45916574-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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:

EPG5 (HGNC:):

EPG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 466245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45916574-G-A is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPG5	NM_020964.3 linkuse as main transcript	c.3248C>T	p.Ser1083Leu	missense_variant	18/44	ENST00000282041.11	NP_066015.2	Q9HCE0-1Q9BTI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000282041.11 linkuse as main transcript	c.3248C>T	p.Ser1083Leu	missense_variant	18/44	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

GnomAD3 exomes

AF:

0.0266

AC:

6592

AN:

247554

Hom.:

142

AF XY:

0.0285

AC XY:

3820

AN XY:

134254

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 SAS exome

AF:

0.0479

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

Gnomad4 AFR exome

AF:

0.00494

Gnomad4 AMR exome

AF:

0.00735

Gnomad4 ASJ exome

AF:

0.0241

Gnomad4 EAS exome

AF:

0.00322

Gnomad4 SAS exome

AF:

0.0487

Gnomad4 FIN exome

AF:

0.0396

Gnomad4 NFE exome

AF:

0.0314

Gnomad4 OTH exome

AF:

0.0260

GnomAD4 genome

AF:

0.0214

AC:

3256

AN:

152170

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1606

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00643

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.00252

Gnomad4 SAS

AF:

0.0415

Gnomad4 FIN

AF:

0.0363

Gnomad4 NFE

AF:

0.0307

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0273

Hom.:

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

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Vici syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

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

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

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

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