rs1779297

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The ENST00000367324.8(PKP1):​c.780G>A​(p.Lys260=) 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
ENST00000367324.8 synonymous

Scores

1

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.38
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
PKP1NM_001005337.3 linkuse as main transcriptc.780G>A p.Lys260= synonymous_variant 4/14 ENST00000367324.8 NP_001005337.1
PKP1NM_000299.4 linkuse as main transcriptc.780G>A p.Lys260= synonymous_variant 4/15 NP_000290.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PKP1ENST00000367324.8 linkuse as main transcriptc.780G>A p.Lys260= synonymous_variant 4/141 NM_001005337.3 ENSP00000356293 P1Q13835-2
PKP1ENST00000263946.7 linkuse as main transcriptc.780G>A p.Lys260= synonymous_variant 4/155 ENSP00000263946 Q13835-1
PKP1ENST00000352845.3 linkuse as main transcriptc.780G>A p.Lys260= synonymous_variant 4/145 ENSP00000295597 Q13835-1
PKP1ENST00000475988.1 linkuse as main transcriptn.122G>A non_coding_transcript_exon_variant 2/53

Frequencies

GnomAD3 genomes
AF:
0.0295
AC:
4483
AN:
152200
Hom.:
194
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1779297; hg19: chr1-201285759; API