Variant 11-392702-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001303029.2(PKP3):c.75G>A(p.Thr25Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,286,140 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 12 hom. )

Consequence

PKP3
NM_001303029.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.126

Variant links:

Genes affected

PKP3 (HGNC:9025): (plakophilin 3) 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 act in cellular desmosome-dependent adhesion and signaling pathways. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

PKP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-392702-G-A is Benign according to our data. Variant chr11-392702-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641043.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.126 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP3	NM_001303029.2 linkuse as main transcript	c.75G>A	p.Thr25Thr	synonymous_variant	1/14		NP_001289958.1	Q9Y446-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP3	ENST00000534401.5 linkuse as main transcript	c.75G>A	p.Thr25Thr	synonymous_variant	1/4	3		ENSP00000434517.3		E9PQ15

Frequencies

GnomAD3 genomes

AF:

0.00416

AC:

632

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00688

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00315

AC:

403

AN:

127938

Hom.:

AF XY:

0.00288

AC XY:

202

AN XY:

70066

show subpopulations

Gnomad AFR exome

AF:

0.00214

Gnomad AMR exome

AF:

0.00259

Gnomad ASJ exome

AF:

0.00211

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000447

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00577

GnomAD4 exome

AF:

0.00486

AC:

5514

AN:

1133992

Hom.:

Cov.:

AF XY:

0.00460

AC XY:

2557

AN XY:

556314

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00276

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000289

Gnomad4 FIN exome

AF:

0.00111

Gnomad4 NFE exome

AF:

0.00556

Gnomad4 OTH exome

AF:

0.00489

GnomAD4 genome

AF:

0.00415

AC:

631

AN:

152148

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

285

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00689

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.00468

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

PKP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.4

DANN

Benign

0.54

Splicing

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