Variant 18-45866897-C-T 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 NM_020964.3(EPG5):c.6522G>A(p.Pro2174Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,613,994 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 8 hom., cov: 32)

Exomes 𝑓: 0.011 ( 103 hom. )

Consequence

EPG5
NM_020964.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.13

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 18-45866897-C-T is Benign according to our data. Variant chr18-45866897-C-T is described in ClinVar as [Benign]. Clinvar id is 534619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.13 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.007 (1066/152268) while in subpopulation NFE AF= 0.0116 (791/68022). AF 95% confidence interval is 0.011. There are 8 homozygotes in gnomad4. There are 504 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPG5	NM_020964.3 linkuse as main transcript	c.6522G>A	p.Pro2174Pro	synonymous_variant	38/44	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.6522G>A	p.Pro2174Pro	synonymous_variant	38/44	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.00701

AC:

1066

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00677

AC:

1688

AN:

249492

Hom.:

AF XY:

0.00699

AC XY:

946

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00768

Gnomad FIN exome

AF:

0.00515

Gnomad NFE exome

AF:

0.00996

Gnomad OTH exome

AF:

0.00643

GnomAD4 exome

AF:

0.0106

AC:

15527

AN:

1461726

Hom.:

103

Cov.:

AF XY:

0.0105

AC XY:

7654

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00329

Gnomad4 ASJ exome

AF:

0.00532

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00685

Gnomad4 FIN exome

AF:

0.00490

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.00700

AC:

1066

AN:

152268

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

504

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00945

Hom.:

Bravo

AF:

0.00657

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0125

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	EPG5: BP4, BP7, BS1, BS2 -
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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.061

DANN

Benign

0.45

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