1-201316631-G-A

Variant names:

• chr1-201316631-G-A
• rs1779297
• NM_001005337.3:c.780G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001005337.3(PKP1):​c.780G>A​(p.Lys260Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 1,613,590 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (194 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (213 hom.)
• Consequence: PKP1 NM_001005337.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38
• Publications: 16 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: Ambry Genetics, G2P, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-201316631-G-A is Benign according to our data. Variant chr1-201316631-G-A is described in ClinVar as Benign. ClinVar VariationId is 775638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0935 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP1	NM_001005337.3	MANE Select	c.780G>A	p.Lys260Lys	synonymous	Exon 4 of 14	NP_001005337.1
	PKP1	NM_000299.4		c.780G>A	p.Lys260Lys	synonymous	Exon 4 of 15	NP_000290.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP1	ENST00000367324.8	TSL:1 MANE Select	c.780G>A	p.Lys260Lys	synonymous	Exon 4 of 14	ENSP00000356293.4
	PKP1	ENST00000263946.7	TSL:5	c.780G>A	p.Lys260Lys	synonymous	Exon 4 of 15	ENSP00000263946.3
	PKP1	ENST00000352845.3	TSL:5	c.780G>A	p.Lys260Lys	synonymous	Exon 4 of 14	ENSP00000295597.3

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4483 AN: 152200 Hom.: 194 Cov.: 33

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.00454 AC: 6634 AN: 1461272 Hom.: 213 Cov.: 33 AF XY: 0.00431 AC XY: 3130 AN XY: 726836

African (AFR) AF: 0.101 AC: 3383 AN: 33474

American (AMR) AF: 0.00755 AC: 337 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0200 AC: 523 AN: 26110

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00631 AC: 543 AN: 86022

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.0143 AC: 82 AN: 5722

European-Non Finnish (NFE) AF: 0.00107 AC: 1195 AN: 1111814

Other (OTH) AF: 0.00942 AC: 569 AN: 60378

GnomAD4 genome AF: 0.0295 AC: 4491 AN: 152318 Hom.: 194 Cov.: 33 AF XY: 0.0284 AC XY: 2115 AN XY: 74484

African (AFR) AF: 0.0960 AC: 3989 AN: 41552

American (AMR) AF: 0.0152 AC: 233 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 68032

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.0145 Hom.: 53

Bravo AF: 0.0332

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1779297; hg19: chr1-201285759;