dbSNP rs11748: PKP3:p.Pro705Pro (chr11-403980-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007183.4(PKP3):c.2115G>A(p.Pro705Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,607,308 control chromosomes in the GnomAD database, including 248,427 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 22978 hom., cov: 33)

Exomes 𝑓: 0.55 ( 225449 hom. )

Consequence

PKP3
NM_007183.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.96

Publications

28 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-3.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP3	NM_007183.4 link	c.2115G>A	p.Pro705Pro	synonymous_variant	Exon 11 of 13	ENST00000331563.7	NP_009114.1	Q9Y446-1
PKP3	NM_001303029.2 link	c.2160G>A	p.Pro720Pro	synonymous_variant	Exon 12 of 14		NP_001289958.1	Q9Y446-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKP3	ENST00000331563.7 link	c.2115G>A	p.Pro705Pro	synonymous_variant	Exon 11 of 13	1	NM_007183.4	ENSP00000331678.2		Q9Y446-1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83095

AN:

151922

Hom.:

22959

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.594

Gnomad ASJ

AF:

0.666

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.558

GnomAD2 exomes

AF:

0.562

AC:

137958

AN:

245466

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.531

Gnomad AMR exome

AF:

0.663

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.364

Gnomad FIN exome

AF:

0.506

Gnomad NFE exome

AF:

0.563

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.554

AC:

806311

AN:

1455268

Hom.:

225449

Cov.:

AF XY:

0.556

AC XY:

402043

AN XY:

723252

show subpopulations

African (AFR)

AF:

0.524

AC:

17481

AN:

33392

American (AMR)

AF:

0.654

AC:

29013

AN:

44346

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

17043

AN:

25968

East Asian (EAS)

AF:

0.329

AC:

13036

AN:

39578

South Asian (SAS)

AF:

0.584

AC:

50162

AN:

85910

European-Finnish (FIN)

AF:

0.507

AC:

26327

AN:

51888

Middle Eastern (MID)

AF:

0.616

AC:

3532

AN:

5738

European-Non Finnish (NFE)

AF:

0.556

AC:

616395

AN:

1108360

Other (OTH)

AF:

0.555

AC:

33322

AN:

60088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

19038

38076

57113

76151

95189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17252

34504

51756

69008

86260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.547

AC:

83162

AN:

152040

Hom.:

22978

Cov.:

AF XY:

0.546

AC XY:

40609

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.527

AC:

21834

AN:

41446

American (AMR)

AF:

0.594

AC:

9092

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.666

AC:

2314

AN:

3472

East Asian (EAS)

AF:

0.372

AC:

1919

AN:

5162

South Asian (SAS)

AF:

0.562

AC:

2714

AN:

4826

European-Finnish (FIN)

AF:

0.511

AC:

5408

AN:

10582

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.558

AC:

37930

AN:

67944

Other (OTH)

AF:

0.562

AC:

1184

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1958

3917

5875

7834

9792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.564

Hom.:

35841

Bravo

AF:

0.553

Asia WGS

AF:

0.459

AC:

1596

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.034

(source)

DANN

Benign

0.80

PhyloP100

-4.0

PromoterAI

0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over