NM_031308.4:c.7119C>T

Variant names:

• chr8-143866135-G-A
• NM_031308.4:c.7119C>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.7119C>T​(p.Asn2373Asn) 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: not found (cov: 1)
  • Exomes 𝑓: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPPK1 NM_031308.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.400
• 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=-0.68).
• BP6: Variant 8-143866135-G-A is Benign according to our data. Variant chr8-143866135-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3051806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.4 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.7119C>T	p.Asn2373Asn	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.7119C>T	p.Asn2373Asn	synonymous	Exon 2 of 2	ENSP00000484472.1	P58107
	EPPK1	ENST00000568225.2	TSL:6	c.7044C>T	p.Asn2348Asn	synonymous	Exon 1 of 1	ENSP00000456124.2	A0A075B730
	ENSG00000305900	ENST00000813856.1		n.157+12952C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249624 AF XY: 0.00

Gnomad AFR exome AF: 0.0000640

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000277 AC: 1 AN: 361510 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 190382

African (AFR) AF: 0.00 AC: 0 AN: 10178

American (AMR) AF: 0.00 AC: 0 AN: 13998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11100

East Asian (EAS) AF: 0.00 AC: 0 AN: 22916

South Asian (SAS) AF: 0.00 AC: 0 AN: 42284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1604

European-Non Finnish (NFE) AF: 0.00000465 AC: 1 AN: 215152

Other (OTH) AF: 0.00 AC: 0 AN: 20910

GnomAD4 genome Cov.: 1

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	-0.68
CADD	Benign	2.0
DANN	Benign	0.97
PhyloP100		0.40

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

hg19: chr8-144995469; COSMIC: COSV73262211;