1-201293304-C-T

Position:

• chr1-201293304-C-T

Variant summary

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

The NM_001005337.3(PKP1):​c.203-638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,204 control chromosomes in the GnomAD database, including 3,809 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 0.20 (3809 hom., cov: 32)
• Consequence: PKP1 NM_001005337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP1	NM_001005337.3	c.203-638C>T		intron_variant		ENST00000367324.8	NP_001005337.1
PKP1	NM_000299.4	c.203-638C>T		intron_variant			NP_000290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP1	ENST00000367324.8	c.203-638C>T		intron_variant		1	NM_001005337.3	ENSP00000356293.4
PKP1	ENST00000263946.7	c.203-638C>T		intron_variant		5		ENSP00000263946.3
PKP1	ENST00000352845.3	c.203-638C>T		intron_variant		5		ENSP00000295597.3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30924 AN: 152084 Hom.: 3812 Cov.: 32

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.203 AC: 30920 AN: 152204 Hom.: 3809 Cov.: 32 AF XY: 0.199 AC XY: 14826 AN XY: 74404

Gnomad4 AFR AF: 0.0745

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.259

Alfa AF: 0.261 Hom.: 9920

Bravo AF: 0.205

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.70

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: rs860554; hg19: chr1-201262432;