Genetic Variant EPPK1:p.Gly2346Gly (chr8-143866216-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_031308.4(EPPK1):c.7038C>T(p.Gly2346Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 3)

Exomes 𝑓: 0.00011 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

EPPK1
NM_031308.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.78

Publications

0 publications found

Variant links:

Genes affected

EPPK1 (HGNC:15577): (epiplakin 1) The protein encoded by this gene belongs to the plakin family of proteins, which play a role in the organization of cytoskeletal architecture. This family member is composed of several highly homologous plakin repeats. It may function to maintain the integrity of keratin intermediate filament networks in epithelial cells. Studies of the orthologous mouse protein suggest that it accelerates keratinocyte migration during wound healing. [provided by RefSeq, Oct 2013]

EPPK1 links:

ENSG00000305900 (HGNC:):

ENSG00000305900 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 8-143866216-G-A is Benign according to our data. Variant chr8-143866216-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3051969.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.78 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031308.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPPK1	NM_031308.4	MANE Select	c.7038C>T	p.Gly2346Gly	synonymous	Exon 2 of 2	NP_112598.3	P58107

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPPK1	ENST00000615648.2	TSL:5 MANE Select	c.7038C>T	p.Gly2346Gly	synonymous	Exon 2 of 2	ENSP00000484472.1	P58107
EPPK1	ENST00000568225.2	TSL:6	c.6963C>T	p.Gly2321Gly	synonymous	Exon 1 of 1	ENSP00000456124.2	A0A075B730
ENSG00000305900	ENST00000813856.1		n.157+12871C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

11248

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

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248734

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000114

AC:

AN:

439890

Hom.:

Cov.:

AF XY:

0.0000864

AC XY:

AN XY:

231588

show subpopulations

African (AFR)

AF:

0.0000834

AC:

AN:

11992

American (AMR)

AF:

0.00169

AC:

AN:

17804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13348

East Asian (EAS)

AF:

0.000233

AC:

AN:

30072

South Asian (SAS)

AF:

0.000111

AC:

AN:

45040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1912

European-Non Finnish (NFE)

AF:

0.0000226

AC:

AN:

265218

Other (OTH)

AF:

0.0000395

AC:

AN:

25332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

11260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4770

African (AFR)

AF:

0.00

AC:

AN:

2424

American (AMR)

AF:

0.00

AC:

AN:

1388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

358

East Asian (EAS)

AF:

0.00

AC:

AN:

822

South Asian (SAS)

AF:

0.00

AC:

AN:

660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5048

Other (OTH)

AF:

0.00

AC:

AN:

228

Alfa

AF:

0.000169

Hom.:

Bravo

AF:

0.000147

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

EPPK1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.9

(source)

DANN

Benign

0.96

PhyloP100

-2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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