Genetic Variant EPPK1:p.Ala4933Ala (chr8-143858455-C-T) – 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.14799G>A(p.Ala4933Ala) 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: 9)

Exomes 𝑓: 0.000024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPPK1
NM_031308.4 synonymous

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -11.4

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 (Cadd=7.504).

BP6

Variant 8-143858455-C-T is Benign according to our data. Variant chr8-143858455-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2658923.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-11.4 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.14799G>A	p.Ala4933Ala	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.14799G>A	p.Ala4933Ala	synonymous	Exon 2 of 2	ENSP00000484472.1	P58107
EPPK1	ENST00000568225.2	TSL:6	c.14724G>A	p.Ala4908Ala	synonymous	Exon 1 of 1	ENSP00000456124.2	A0A075B730
ENSG00000305900	ENST00000813856.1		n.158-12591G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

75050

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000240

AC:

AN:

625370

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

321052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15062

American (AMR)

AF:

0.00

AC:

AN:

21216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15262

East Asian (EAS)

AF:

0.00

AC:

AN:

31600

South Asian (SAS)

AF:

0.0000200

AC:

AN:

50088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2330

European-Non Finnish (NFE)

AF:

0.0000327

AC:

AN:

428392

Other (OTH)

AF:

0.00

AC:

AN:

31662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

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;AS_VQSR

AF:

0.00

AC:

AN:

75050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33062

African (AFR)

AF:

0.00

AC:

AN:

14944

American (AMR)

AF:

0.00

AC:

AN:

7282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2140

East Asian (EAS)

AF:

0.00

AC:

AN:

2980

South Asian (SAS)

AF:

0.00

AC:

AN:

1996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

39680

Other (OTH)

AF:

0.00

AC:

AN:

938

Alfa

AF:

0.0000302

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

CADD

Benign

7.5

(source)

PhyloP100

-11

Splicing

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

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