1-201293304-C-T

Variant names:

• chr1-201293304-C-T
• rs860554
• NM_001005337.3:c.203-638C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

PKP1 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex due to plakophilin deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005337.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP1	NM_001005337.3	MANE Select	c.203-638C>T		intron	N/A	NP_001005337.1	Q13835-2
	PKP1	NM_000299.4		c.203-638C>T		intron	N/A	NP_000290.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP1	ENST00000367324.8	TSL:1 MANE Select	c.203-638C>T		intron	N/A	ENSP00000356293.4	Q13835-2
	PKP1	ENST00000263946.7	TSL:5	c.203-638C>T		intron	N/A	ENSP00000263946.3	Q13835-1
	PKP1	ENST00000352845.3	TSL:5	c.203-638C>T		intron	N/A	ENSP00000295597.3	Q13835-1

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

African (AFR) AF: 0.0745 AC: 3097 AN: 41558

American (AMR) AF: 0.235 AC: 3591 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3468

East Asian (EAS) AF: 0.150 AC: 774 AN: 5176

South Asian (SAS) AF: 0.128 AC: 617 AN: 4818

European-Finnish (FIN) AF: 0.189 AC: 2001 AN: 10594

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18897 AN: 67982

Other (OTH) AF: 0.259 AC: 547 AN: 2114

Alfa AF: 0.252 Hom.: 19474

Bravo AF: 0.205

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs860554; hg19: chr1-201262432;