rs832147

Positions:

• chr1-201300559-C-G

Variant summary

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

The NM_001005337.3(PKP1):​c.306+6514C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,222 control chromosomes in the GnomAD database, including 2,496 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 0.17 (2496 hom., cov: 33)
• Consequence: PKP1 NM_001005337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

Genes affected

PKP1 (HGNC:9023): (plakophilin 1) 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 be involved in molecular recruitment and stabilization during desmosome formation. Mutations in this gene have been associated with the ectodermal dysplasia/skin fragility syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP1	NM_001005337.3	c.306+6514C>G		intron_variant		ENST00000367324.8	NP_001005337.1
PKP1	NM_000299.4	c.306+6514C>G		intron_variant			NP_000290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP1	ENST00000367324.8	c.306+6514C>G		intron_variant		1	NM_001005337.3	ENSP00000356293	P1
PKP1	ENST00000263946.7	c.306+6514C>G		intron_variant		5		ENSP00000263946
PKP1	ENST00000352845.3	c.306+6514C>G		intron_variant		5		ENSP00000295597

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25671 AN: 152104 Hom.: 2494 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25682 AN: 152222 Hom.: 2496 Cov.: 33 AF XY: 0.167 AC XY: 12412 AN XY: 74430

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.189

Alfa AF: 0.187 Hom.: 361

Bravo AF: 0.172

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.78

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: rs832147; hg19: chr1-201269687;