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: ClinGen, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

EPG5 links:

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ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020964.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPG5	NM_020964.3	MANE Select	c.6622-13_6622-7dupTTTTTTT	splice_region intron	N/A	NP_066015.2	Q9HCE0-1
EPG5	NM_001410859.1		c.6619-13_6619-7dupTTTTTTT	splice_region intron	N/A	NP_001397788.1	A0A8Q3SIU6
EPG5	NM_001410858.1		c.6622-13_6622-7dupTTTTTTT	splice_region intron	N/A	NP_001397787.1	A0A8Q3SIJ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPG5	ENST00000282041.11	TSL:1 MANE Select	c.6622-7_6622-6insTTTTTTT	splice_region intron	N/A	ENSP00000282041.4	Q9HCE0-1
EPG5	ENST00000587884.2	TSL:1	n.2362-7_2362-6insTTTTTTT	splice_region intron	N/A	ENSP00000466990.2	K7ENK5
EPG5	ENST00000590884.6	TSL:1	n.934-7_934-6insTTTTTTT	splice_region intron	N/A	ENSP00000466403.2	K7EM87

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), 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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over