rs1779297

Positions:

• chr1-201316631-G-A
• chr1-201316631-G-C
• chr1-201316631-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKP1	NM_001005337.3	c.780G>A	p.Lys260Lys	synonymous_variant	4/14	ENST00000367324.8	NP_001005337.1
PKP1	NM_000299.4	c.780G>A	p.Lys260Lys	synonymous_variant	4/15		NP_000290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKP1	ENST00000367324.8	c.780G>A	p.Lys260Lys	synonymous_variant	4/14	1	NM_001005337.3	ENSP00000356293.4
PKP1	ENST00000263946.7	c.780G>A	p.Lys260Lys	synonymous_variant	4/15	5		ENSP00000263946.3
PKP1	ENST00000352845.3	c.780G>A	p.Lys260Lys	synonymous_variant	4/14	5		ENSP00000295597.3
PKP1	ENST00000475988.1	n.122G>A		non_coding_transcript_exon_variant	2/5	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

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00755

Gnomad4 ASJ exome AF: 0.0200

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00631

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00107

Gnomad4 OTH exome AF: 0.00942

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

Gnomad4 AFR AF: 0.0960

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0148 Hom.: 39

Bravo AF: 0.0332

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1779297; hg19: chr1-201285759;