Genetic Variant EPG5:c.6622-8_6622-7dupTT (chr18-45865765-C-CAA) – 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.6622-8_6622-7dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,407,766 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 0.00019 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0019 ( 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.6622-8_6622-7dupTT	splice_region intron	N/A	NP_066015.2	Q9HCE0-1
EPG5	NM_001410859.1		c.6619-8_6619-7dupTT	splice_region intron	N/A	NP_001397788.1	A0A8Q3SIU6
EPG5	NM_001410858.1		c.6622-8_6622-7dupTT	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_6622-6insTT	splice_region intron	N/A	ENSP00000282041.4	Q9HCE0-1
EPG5	ENST00000587884.2	TSL:1	n.2362-7_2362-6insTT	splice_region intron	N/A	ENSP00000466990.2	K7ENK5
EPG5	ENST00000590884.6	TSL:1	n.934-7_934-6insTT	splice_region intron	N/A	ENSP00000466403.2	K7EM87

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

102554

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000352

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000960

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000189

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00723

AC:

757

AN:

104766

AF XY:

0.00757

show subpopulations

Gnomad AFR exome

AF:

0.00841

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00340

Gnomad EAS exome

AF:

0.00647

Gnomad FIN exome

AF:

0.00665

Gnomad NFE exome

AF:

0.00894

Gnomad OTH exome

AF:

0.00714

GnomAD4 exome

AF:

0.00195

AC:

2543

AN:

1305202

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1280

AN XY:

645520

show subpopulations

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

African (AFR)

AF:

0.00173

AC:

AN:

28298

American (AMR)

AF:

0.00218

AC:

AN:

30710

Ashkenazi Jewish (ASJ)

AF:

0.00141

AC:

AN:

20570

East Asian (EAS)

AF:

0.00152

AC:

AN:

37486

South Asian (SAS)

AF:

0.00219

AC:

149

AN:

67922

European-Finnish (FIN)

AF:

0.00278

AC:

104

AN:

37458

Middle Eastern (MID)

AF:

0.00189

AC:

AN:

4228

European-Non Finnish (NFE)

AF:

0.00194

AC:

1984

AN:

1024240

Other (OTH)

AF:

0.00177

AC:

AN:

54290

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.306

Heterozygous variant carriers

212

425

637

850

1062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.000185

AC:

AN:

102564

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

AN XY:

49282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25200

American (AMR)

AF:

0.000352

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:

0.000960

AC:

AN:

6252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

154

European-Non Finnish (NFE)

AF:

0.000189

AC:

AN:

47564

Other (OTH)

AF:

0.00

AC:

AN:

1440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

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-CAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over