chr8-143866447-G-C

Variant names:

• chr8-143866447-G-C
• rs1442851164
• NM_031308.4:c.6807C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_031308.4(EPPK1):​c.6807C>G​(p.Thr2269Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T2269T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPPK1 NM_031308.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.61
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• 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>G	p.Thr2269Thr	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.6807C>G	p.Thr2269Thr	synonymous	Exon 2 of 2	ENSP00000484472.1	P58107
	EPPK1	ENST00000568225.2	TSL:6	c.6732C>G	p.Thr2244Thr	synonymous	Exon 1 of 1	ENSP00000456124.2	A0A075B730
	ENSG00000305900	ENST00000813856.1		n.157+12640C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1261068 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 620260

African (AFR) AF: 0.00 AC: 0 AN: 28980

American (AMR) AF: 0.00 AC: 0 AN: 29352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20868

East Asian (EAS) AF: 0.00 AC: 0 AN: 35920

South Asian (SAS) AF: 0.00 AC: 0 AN: 70346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 986622

Other (OTH) AF: 0.00 AC: 0 AN: 53074

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.4
DANN	Benign	0.81
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

Other links and lift over

dbSNP: rs1442851164; hg19: chr8-144940615;