Variant rs72918350 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000282041.11(EPG5):c.3279C>T(p.Ser1093=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,610,766 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 13 hom., cov: 32)

Exomes 𝑓: 0.012 ( 134 hom. )

Consequence

EPG5
ENST00000282041.11 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.424

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 18-45916543-G-A is Benign according to our data. Variant chr18-45916543-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 466246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-45916543-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.424 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00877 (1335/152242) while in subpopulation NFE AF= 0.014 (952/68000). AF 95% confidence interval is 0.0133. There are 13 homozygotes in gnomad4. There are 650 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPG5	NM_020964.3 linkuse as main transcript	c.3279C>T	p.Ser1093=	synonymous_variant	18/44	ENST00000282041.11	NP_066015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPG5	ENST00000282041.11 linkuse as main transcript	c.3279C>T	p.Ser1093=	synonymous_variant	18/44	1	NM_020964.3	ENSP00000282041	P4	Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.00878

AC:

1336

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0160

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.00815

GnomAD3 exomes

AF:

0.00954

AC:

2376

AN:

249160

Hom.:

AF XY:

0.00942

AC XY:

1273

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.00592

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00284

Gnomad FIN exome

AF:

0.0155

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.00958

GnomAD4 exome

AF:

0.0124

AC:

18099

AN:

1458524

Hom.:

134

Cov.:

AF XY:

0.0121

AC XY:

8790

AN XY:

724758

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.00575

Gnomad4 ASJ exome

AF:

0.00613

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00306

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00877

AC:

1335

AN:

152242

Hom.:

Cov.:

AF XY:

0.00873

AC XY:

650

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0160

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00973

Hom.:

Bravo

AF:

0.00822

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0140

EpiControl

AF:

0.0133

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	EPG5: BP4, BP7, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 23, 2019	- -

EPG5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Vici syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.9

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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