1-201317643-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001005337.3(PKP1):c.918C>T(p.Ala306Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,613,656 control chromosomes in the GnomAD database, including 34,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2818 hom., cov: 32)

Exomes 𝑓: 0.21 ( 32099 hom. )

Consequence

PKP1
NM_001005337.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -8.92

Variant links:

Genes affected

PKP1 (HGNC:9023): (plakophilin 1) This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This protein may be involved in molecular recruitment and stabilization during desmosome formation. Mutations in this gene have been associated with the ectodermal dysplasia/skin fragility syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

PKP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 1-201317643-C-T is Benign according to our data. Variant chr1-201317643-C-T is described in ClinVar as [Benign]. Clinvar id is 256862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-201317643-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-8.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP1	NM_001005337.3 link	c.918C>T	p.Ala306Ala	synonymous_variant	Exon 5 of 14	ENST00000367324.8	NP_001005337.1	Q13835-2A0A024R952
PKP1	NM_000299.4 link	c.918C>T	p.Ala306Ala	synonymous_variant	Exon 5 of 15		NP_000290.2	Q13835-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PKP1	ENST00000367324.8 link	c.918C>T	p.Ala306Ala	synonymous_variant	Exon 5 of 14	1	NM_001005337.3	ENSP00000356293.4	Q13835-2
PKP1	ENST00000263946.7 link	c.918C>T	p.Ala306Ala	synonymous_variant	Exon 5 of 15	5		ENSP00000263946.3	Q13835-1
PKP1	ENST00000352845.3 link	c.918C>T	p.Ala306Ala	synonymous_variant	Exon 5 of 14	5		ENSP00000295597.3	Q13835-1
PKP1	ENST00000475988.1 link	n.260C>T		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28382

AN:

151992

Hom.:

2807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.196

AC:

48831

AN:

249448

Hom.:

5025

AF XY:

0.193

AC XY:

26051

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.206

AC:

301799

AN:

1461548

Hom.:

32099

Cov.:

AF XY:

0.204

AC XY:

148058

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.225

Gnomad4 ASJ exome

AF:

0.160

Gnomad4 EAS exome

AF:

0.236

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.187

AC:

28441

AN:

152108

Hom.:

2818

Cov.:

AF XY:

0.184

AC XY:

13700

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.199

Hom.:

1798

Bravo

AF:

0.193

Asia WGS

AF:

0.188

AC:

655

AN:

3478

EpiCase

AF:

0.216

EpiControl

AF:

0.217

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epidermolysis bullosa simplex due to plakophilin deficiency

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.42

DANN

Benign

0.71

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over