1-201283738-C-T

Position:

chr1-201283738-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001005337.3(PKP1):c.36C>T(p.Tyr12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,613,826 control chromosomes in the GnomAD database, including 11,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2957 hom., cov: 33)

Exomes 𝑓: 0.097 ( 8539 hom. )

Consequence

PKP1
NM_001005337.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.822

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 1-201283738-C-T is Benign according to our data. Variant chr1-201283738-C-T is described in ClinVar as [Benign]. Clinvar id is 256861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.822 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP1	NM_001005337.3 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/14	ENST00000367324.8	NP_001005337.1
PKP1	NM_000299.4 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/15		NP_000290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP1	ENST00000367324.8 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/14	1	NM_001005337.3	ENSP00000356293	P1	Q13835-2
PKP1	ENST00000263946.7 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/15	5		ENSP00000263946		Q13835-1
PKP1	ENST00000352845.3 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/14	5		ENSP00000295597		Q13835-1

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25052

AN:

152068

Hom.:

2952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.0805

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.0861

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.116

AC:

29039

AN:

250988

Hom.:

2310

AF XY:

0.113

AC XY:

15321

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.0928

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.0746

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.0844

Gnomad OTH exome

AF:

0.0986

GnomAD4 exome

AF:

0.0975

AC:

142472

AN:

1461640

Hom.:

8539

Cov.:

AF XY:

0.0983

AC XY:

71494

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.347

Gnomad4 AMR exome

AF:

0.0969

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.0781

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.0842

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.165

AC:

25072

AN:

152186

Hom.:

2957

Cov.:

AF XY:

0.164

AC XY:

12221

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.0801

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.0861

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.104

Hom.:

1960

Bravo

AF:

0.167

Asia WGS

AF:

0.159

AC:

554

AN:

3478

EpiCase

AF:

0.0839

EpiControl

AF:

0.0841

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epidermolysis bullosa simplex due to plakophilin deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.43

CADD

Benign

DANN

Benign

0.96

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