chr8-143866052-A-G

Position:

• chr8-143866052-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_031308.4(EPPK1):​c.7202T>C​(p.Leu2401Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: EPPK1 NM_031308.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.564

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPPK1	NM_031308.4	c.7202T>C	p.Leu2401Pro	missense_variant	2/2	ENST00000615648.2	NP_112598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPPK1	ENST00000615648.2	c.7202T>C	p.Leu2401Pro	missense_variant	2/2	5	NM_031308.4	ENSP00000484472	A2
EPPK1	ENST00000568225.2	c.7127T>C	p.Leu2376Pro	missense_variant	1/1			ENSP00000456124	P4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.7202T>C (p.L2401P) alteration is located in exon 1 (coding exon 1) of the EPPK1 gene. This alteration results from a T to C substitution at nucleotide position 7202, causing the leucine (L) at amino acid position 2401 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
CADD	Uncertain	24
DEOGEN2	Uncertain	0.61	D;.
LIST_S2	Uncertain	0.94	D;D
MetaRNN	Uncertain	0.71	D;D
PROVEAN	Uncertain	-4.2	.;D
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.0040	D;D
Vest4		0.67
gMVP		0.95

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: -;