Genetic Variant EPPK1:p.Thr2269Thr (chr8-143866447-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_031308.4(EPPK1):c.6807C>T(p.Thr2269Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000686 in 1,399,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

EPPK1
NM_031308.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.61

Publications

2 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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 8-143866447-G-A is Benign according to our data. Variant chr8-143866447-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3039843.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.61 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.6807C>T	p.Thr2269Thr	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.6807C>T	p.Thr2269Thr	synonymous	Exon 2 of 2	ENSP00000484472.1	P58107
EPPK1	ENST00000568225.2	TSL:6	c.6732C>T	p.Thr2244Thr	synonymous	Exon 1 of 1	ENSP00000456124.2	A0A075B730
ENSG00000305900	ENST00000813856.1		n.157+12640C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000101

AC:

AN:

138736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000216

Gnomad SAS

AF:

0.000265

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.0000936

Gnomad OTH

AF:

0.000551

GnomAD2 exomes

AF:

0.0000205

AC:

AN:

243714

AF XY:

0.0000301

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1261066

Hom.:

Cov.:

AF XY:

0.0000790

AC XY:

AN XY:

620258

show subpopulations

African (AFR)

AF:

0.000104

AC:

AN:

28980

American (AMR)

AF:

0.0000681

AC:

AN:

29352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20868

East Asian (EAS)

AF:

0.0000557

AC:

AN:

35920

South Asian (SAS)

AF:

0.000114

AC:

AN:

70346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3730

European-Non Finnish (NFE)

AF:

0.0000628

AC:

AN:

986620

Other (OTH)

AF:

0.0000942

AC:

AN:

53074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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

AF:

0.000101

AC:

AN:

138852

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

67022

show subpopulations

African (AFR)

AF:

0.000109

AC:

AN:

36798

American (AMR)

AF:

0.00

AC:

AN:

13872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3326

East Asian (EAS)

AF:

0.000216

AC:

AN:

4624

South Asian (SAS)

AF:

0.000266

AC:

AN:

3766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9406

Middle Eastern (MID)

AF:

0.00357

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000936

AC:

AN:

64096

Other (OTH)

AF:

0.000545

AC:

AN:

1836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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.:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

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

-0.67

CADD

Benign

6.8

(source)

DANN

Benign

0.95

PhyloP100

-5.6

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over