Genetic Variant EPG5:c.6622-22_6622-7dupTTTTTTTTTTTTTTTT (chr18-45865765-C-CAAAAAAAAAAAAAAAA) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_020964.3(EPG5):c.6622-22_6622-7dupTTTTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPG5
NM_020964.3 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.327

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 18-45865765-C-CAAAAAAAAAAAAAAAA is Benign according to our data. Variant chr18-45865765-C-CAAAAAAAAAAAAAAAA is described in ClinVar as Likely_benign. ClinVar VariationId is 2067025.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3 link	c.6622-22_6622-7dupTTTTTTTTTTTTTTTT		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_6622-6insTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

102558

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000382

AC:

AN:

1309294

Hom.:

Cov.:

AF XY:

0.00000463

AC XY:

AN XY:

647534

show subpopulations

African (AFR)

AF:

0.0000705

AC:

AN:

28370

American (AMR)

AF:

0.00

AC:

AN:

30794

Ashkenazi Jewish (ASJ)

AF:

0.0000485

AC:

AN:

20626

East Asian (EAS)

AF:

0.00

AC:

AN:

37546

South Asian (SAS)

AF:

0.00

AC:

AN:

68130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4242

European-Non Finnish (NFE)

AF:

0.00000195

AC:

AN:

1027590

Other (OTH)

AF:

0.00

AC:

AN:

54432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

102568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

49284

African (AFR)

AF:

0.00

AC:

AN:

25200

American (AMR)

AF:

0.00

AC:

AN:

11376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2386

East Asian (EAS)

AF:

0.00

AC:

AN:

3974

South Asian (SAS)

AF:

0.00

AC:

AN:

3628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

154

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

47568

Other (OTH)

AF:

0.00

AC:

AN:

1440

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Vici syndrome

Benign:1

Feb 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.33

Splicing

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

Publications

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18-45865765-CAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over