1-201289391-A-T

Variant summary

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

The NM_001005337.3(PKP1):c.203-4551A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,158 control chromosomes in the GnomAD database, including 36,332 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 0.66 (36332 hom., cov: 32)
• Consequence: PKP1 NM_001005337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKP1	NM_001005337.3	c.203-4551A>T		intron_variant		ENST00000367324.8
PKP1	NM_000299.4	c.203-4551A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKP1	ENST00000367324.8	c.203-4551A>T		intron_variant		1	NM_001005337.3	P1
PKP1	ENST00000263946.7	c.203-4551A>T		intron_variant		5
PKP1	ENST00000352845.3	c.203-4551A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100571 AN: 152040 Hom.: 36318 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.661 AC: 100612 AN: 152158 Hom.: 36332 Cov.: 32 AF XY: 0.664 AC XY: 49356 AN XY: 74382

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.688

Alfa AF: 0.770 Hom.: 22694

Bravo AF: 0.649

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.080
Dann	Benign	0.47

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: rs832174; hg19: chr1-201258519;