Genetic Variant EPG5:c.6622-13_6622-7dupTTTTTTT (chr18-45865765-C-CAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020964.3(EPG5):c.6622-13_6622-7dupTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,411,760 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000097 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

EPG5
NM_020964.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.327

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPG5	NM_020964.3 link	c.6622-13_6622-7dupTTTTTTT		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_6622-6insTTTTTTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.00000975

AC:

AN:

102558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000398

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:

0.0000344

AC:

AN:

1309192

Hom.:

Cov.:

AF XY:

0.0000216

AC XY:

AN XY:

647488

show subpopulations

African (AFR)

AF:

0.000812

AC:

AN:

28320

American (AMR)

AF:

0.0000974

AC:

AN:

30790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20626

East Asian (EAS)

AF:

0.00

AC:

AN:

37546

South Asian (SAS)

AF:

0.0000147

AC:

AN:

68130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37564

Middle Eastern (MID)

AF:

0.000236

AC:

AN:

4240

European-Non Finnish (NFE)

AF:

0.00000973

AC:

AN:

1027568

Other (OTH)

AF:

0.000129

AC:

AN:

54408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.00000975

AC:

AN:

102568

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

49282

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000397

AC:

AN:

25202

American (AMR)

AF:

0.00

AC:

AN:

11374

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

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-CAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over