dbSNP rs913005931: PKP3:p.Gly32Asp (chr11-394387-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007183.4(PKP3):c.95G>A(p.Gly32Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,490,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

PKP3
NM_007183.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15141952).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007183.4. 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
	PKP3	NM_007183.4	MANE Select	c.95G>A	p.Gly32Asp	missense	Exon 1 of 13	NP_009114.1	Q9Y446-1
	PKP3	NM_001303029.2		c.140G>A	p.Gly47Asp	missense	Exon 2 of 14	NP_001289958.1	Q9Y446-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKP3	ENST00000331563.7	TSL:1 MANE Select	c.95G>A	p.Gly32Asp	missense	Exon 1 of 13	ENSP00000331678.2	Q9Y446-1
PKP3	ENST00000534401.6	TSL:3	c.140G>A	p.Gly47Asp	missense	Exon 2 of 14	ENSP00000434517.3	Q9Y446-2
PKP3	ENST00000895790.1		c.95G>A	p.Gly32Asp	missense	Exon 1 of 13	ENSP00000565849.1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000102

AC:

AN:

87898

AF XY:

0.000100

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000229

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000153

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

160

AN:

1338596

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

659530

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26872

American (AMR)

AF:

0.000304

AC:

AN:

29574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23280

East Asian (EAS)

AF:

0.00

AC:

AN:

31084

South Asian (SAS)

AF:

0.00

AC:

AN:

74612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33374

Middle Eastern (MID)

AF:

0.000507

AC:

AN:

3948

European-Non Finnish (NFE)

AF:

0.000124

AC:

131

AN:

1060286

Other (OTH)

AF:

0.000324

AC:

AN:

55566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000197

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41574

American (AMR)

AF:

0.000784

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68000

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000147

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.34

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.4

PhyloP100

2.8

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.087

Sift

Uncertain

0.0090

Sift4G

Pathogenic

0.0

Polyphen

0.099

Vest4

0.17

MutPred

0.26

Loss of helix (P = 0.0093)

MVP

0.61

MPC

0.10

ClinPred

0.065

GERP RS

-0.14

PromoterAI

-0.0050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.18

gMVP

0.37

Mutation Taster

=93/7

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over