Genetic Variant EPG5:c.6622-7dupT (chr18-45865765-C-CA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020964.3(EPG5):c.6622-7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,378,268 control chromosomes in the GnomAD database, including 258 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 227 hom., cov: 25)

Exomes 𝑓: 0.086 ( 31 hom. )

Consequence

EPG5
NM_020964.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.327

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 18-45865765-C-CA is Benign according to our data. Variant chr18-45865765-C-CA is described in ClinVar as [Benign]. Clinvar id is 769442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3 link	c.6622-7dupT		splice_region_variant, intron_variant	Intron 38 of 43	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.6622-7_6622-6insT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.0748

AC:

7663

AN:

102444

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.0564

Gnomad ASJ

AF:

0.0645

Gnomad EAS

AF:

0.00752

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.0907

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0962

GnomAD4 exome

AF:

0.0863

AC:

110101

AN:

1275814

Hom.:

Cov.:

AF XY:

0.0841

AC XY:

53074

AN XY:

630982

show subpopulations

Gnomad4 AFR exome

AF:

0.0507

Gnomad4 AMR exome

AF:

0.0364

Gnomad4 ASJ exome

AF:

0.0544

Gnomad4 EAS exome

AF:

0.0227

Gnomad4 SAS exome

AF:

0.0437

Gnomad4 FIN exome

AF:

0.0622

Gnomad4 NFE exome

AF:

0.0961

Gnomad4 OTH exome

AF:

0.0773

GnomAD4 genome

AF:

0.0748

AC:

7665

AN:

102454

Hom.:

227

Cov.:

AF XY:

0.0719

AC XY:

3541

AN XY:

49226

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.0564

Gnomad4 ASJ

AF:

0.0645

Gnomad4 EAS

AF:

0.00755

Gnomad4 SAS

AF:

0.0254

Gnomad4 FIN

AF:

0.0907

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0951

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 01, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Vici syndrome

Benign:1

Nov 27, 2024

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

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.

18-45865765-CAAAAAAA-CAAAAAAAA

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