rs10902158

chr11-396308-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007183.4(PKP3):c.233-300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 379,624 control chromosomes in the GnomAD database, including 12,435 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 0.24 (5279 hom., cov: 33)
  • Exomes 𝑓: 0.21 (7156 hom.)
• Consequence: PKP3 NM_007183.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKP3	NM_007183.4	c.233-300G>A		intron_variant		ENST00000331563.7
PKP3	NM_001303029.2	c.278-300G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKP3	ENST00000331563.7	c.233-300G>A		intron_variant		1	NM_007183.4	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36340 AN: 151990 Hom.: 5267 Cov.: 33

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.208 AC: 47353 AN: 227516 Hom.: 7156 Cov.: 0 AF XY: 0.209 AC XY: 24168 AN XY: 115802

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.239 AC: 36388 AN: 152108 Hom.: 5279 Cov.: 33 AF XY: 0.240 AC XY: 17856 AN XY: 74374

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.229

Alfa AF: 0.176 Hom.: 2901

Bravo AF: 0.252

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.4
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs10902158; hg19: chr11-396308;