Genetic Variant NM_020964.3:c.6622-10_6622-7delTTTT (chr18-45865765-CAAAA-C) – 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.6622-10_6622-7delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,407,098 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

EPG5
NM_020964.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.635

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:

Genome browser will be placed here

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.6622-10_6622-7delTTTT		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.6622-10_6622-7delTTTT		splice_region_variant, intron_variant	Intron 38 of 43	1	NM_020964.3	ENSP00000282041.4		Q9HCE0-1

Frequencies

GnomAD3 genomes

AF:

0.0000390

AC:

AN:

102552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000795

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:

0.000160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000210

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000228

AC:

297

AN:

1304536

Hom.:

AF XY:

0.000243

AC XY:

157

AN XY:

645178

show subpopulations

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

African (AFR)

AF:

0.000354

AC:

AN:

28250

American (AMR)

AF:

0.000847

AC:

AN:

30680

Ashkenazi Jewish (ASJ)

AF:

0.000535

AC:

AN:

20554

East Asian (EAS)

AF:

0.000321

AC:

AN:

37400

South Asian (SAS)

AF:

0.000443

AC:

AN:

67764

European-Finnish (FIN)

AF:

0.000642

AC:

AN:

37394

Middle Eastern (MID)

AF:

0.000710

AC:

AN:

4224

European-Non Finnish (NFE)

AF:

0.000163

AC:

167

AN:

1024028

Other (OTH)

AF:

0.000258

AC:

AN:

54242

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.252

Heterozygous variant carriers

124

165

206

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

AF:

0.0000390

AC:

AN:

102562

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

49284

show subpopulations

African (AFR)

AF:

0.0000794

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:

0.000160

AC:

AN:

6248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

154

European-Non Finnish (NFE)

AF:

0.0000210

AC:

AN:

47566

Other (OTH)

AF:

0.00

AC:

AN:

1440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over