rs7105848

Positions:

• chr11-396546-G-A
• chr11-396546-G-C

Variant summary

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

The ENST00000331563.7(PKP3):​c.233-62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,171,976 control chromosomes in the GnomAD database, including 35,700 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 0.29 (8350 hom., cov: 34)
  • Exomes 𝑓: 0.20 (27350 hom.)
• Consequence: PKP3 ENST00000331563.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP3	NM_007183.4	c.233-62G>A		intron_variant		ENST00000331563.7	NP_009114.1
PKP3	NM_001303029.2	c.278-62G>A		intron_variant			NP_001289958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP3	ENST00000331563.7	c.233-62G>A		intron_variant		1	NM_007183.4	ENSP00000331678	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43463 AN: 151964 Hom.: 8328 Cov.: 34

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.203 AC: 207092 AN: 1019894 Hom.: 27350 Cov.: 13 AF XY: 0.206 AC XY: 105538 AN XY: 512870

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.602

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.286 AC: 43528 AN: 152082 Hom.: 8350 Cov.: 34 AF XY: 0.286 AC XY: 21300 AN XY: 74352

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.268

Alfa AF: 0.216 Hom.: 1405

Bravo AF: 0.306

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.50
DANN	Benign	0.63

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: rs7105848; hg19: chr11-396546; COSMIC: COSV58990372; COSMIC: COSV58990372;