8-143866216-G-A

Variant names:

• chr8-143866216-G-A
• rs1317058637
• NM_031308.4:c.7038C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.78
• Publications: 0 publications found

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]

ENSG00000305900 (HGNC:):

ACMG classification

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

Sel.	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: 0 AN: 11248 Hom.: 0 Cov.: 3

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: 1 AN: 248734 AF XY: 0.00

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: 50 AN: 439890 Hom.: 1 Cov.: 4 AF XY: 0.0000864 AC XY: 20 AN XY: 231588

African (AFR) AF: 0.0000834 AC: 1 AN: 11992

American (AMR) AF: 0.00169 AC: 30 AN: 17804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13348

East Asian (EAS) AF: 0.000233 AC: 7 AN: 30072

South Asian (SAS) AF: 0.000111 AC: 5 AN: 45040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1912

European-Non Finnish (NFE) AF: 0.0000226 AC: 6 AN: 265218

Other (OTH) AF: 0.0000395 AC: 1 AN: 25332

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 11260 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 4770

African (AFR) AF: 0.00 AC: 0 AN: 2424

American (AMR) AF: 0.00 AC: 0 AN: 1388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 358

East Asian (EAS) AF: 0.00 AC: 0 AN: 822

South Asian (SAS) AF: 0.00 AC: 0 AN: 660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 5048

Other (OTH) AF: 0.00 AC: 0 AN: 228

Alfa AF: 0.000169 Hom.: 0

Bravo AF: 0.000147

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	EPPK1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.9
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

Other links and lift over

dbSNP: rs1317058637; hg19: chr8-144995550;