rs11748

Positions:

• chr11-403980-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.96

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PKP3	NM_007183.4	c.2115G>A	p.Pro705Pro	synonymous_variant	11/13	ENST00000331563.7	NP_009114.1
PKP3	NM_001303029.2	c.2160G>A	p.Pro720Pro	synonymous_variant	12/14		NP_001289958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP3	ENST00000331563.7	c.2115G>A	p.Pro705Pro	synonymous_variant	11/13	1	NM_007183.4	ENSP00000331678.2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83095 AN: 151922 Hom.: 22959 Cov.: 33

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

GnomAD3 exomes AF: 0.562 AC: 137958 AN: 245466 Hom.: 39265 AF XY: 0.563 AC XY: 75108 AN XY: 133480

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 SAS exome AF: 0.581

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.: 52 AF XY: 0.556 AC XY: 402043 AN XY: 723252

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.547 AC: 83162 AN: 152040 Hom.: 22978 Cov.: 33 AF XY: 0.546 AC XY: 40609 AN XY: 74332

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.562

Alfa AF: 0.566 Hom.: 29754

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
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs11748; hg19: chr11-403980; COSMIC: COSV58987299; COSMIC: COSV58987299;