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

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

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 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 rank	MANE	Protein	UniProt
PKP1	NM_001005337.3	c.780G>A	p.Lys260Lys	synonymous_variant	Exon 4 of 14	ENST00000367324.8	NP_001005337.1
PKP1	NM_000299.4	c.780G>A	p.Lys260Lys	synonymous_variant	Exon 4 of 15		NP_000290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKP1	ENST00000367324.8	c.780G>A	p.Lys260Lys	synonymous_variant	Exon 4 of 14	1	NM_001005337.3	ENSP00000356293.4
PKP1	ENST00000263946.7	c.780G>A	p.Lys260Lys	synonymous_variant	Exon 4 of 15	5		ENSP00000263946.3
PKP1	ENST00000352845.3	c.780G>A	p.Lys260Lys	synonymous_variant	Exon 4 of 14	5		ENSP00000295597.3
PKP1	ENST00000475988.1	n.122G>A		non_coding_transcript_exon_variant	Exon 2 of 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 AC: 3383 AN: 33474

Gnomad4 AMR exome AF: 0.00755 AC: 337 AN: 44654

Gnomad4 ASJ exome AF: 0.0200 AC: 523 AN: 26110

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39696

Gnomad4 SAS exome AF: 0.00631 AC: 543 AN: 86022

Gnomad4 FIN exome AF: 0.0000187 AC: 1 AN: 53402

Gnomad4 NFE exome AF: 0.00107 AC: 1195 AN: 1111814

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.0960 AC: 0.0960002 AN: 0.0960002

Gnomad4 AMR AF: 0.0152 AC: 0.0152148 AN: 0.0152148

Gnomad4 ASJ AF: 0.0242 AC: 0.0241935 AN: 0.0241935

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00414 AC: 0.00413907 AN: 0.00413907

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00160 AC: 0.00160219 AN: 0.00160219

Gnomad4 OTH AF: 0.0222 AC: 0.0222327 AN: 0.0222327

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 v4.3

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

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;