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
ENST00000367324.8 synonymous
Scores
1
Clinical Significance
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]
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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 |
---|---|---|---|---|---|---|---|---|
PKP1 | NM_001005337.3 | c.780G>A | p.Lys260= | synonymous_variant | 4/14 | ENST00000367324.8 | NP_001005337.1 | |
PKP1 | NM_000299.4 | c.780G>A | p.Lys260= | 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.Lys260= | synonymous_variant | 4/14 | 1 | NM_001005337.3 | ENSP00000356293 | P1 | |
PKP1 | ENST00000263946.7 | c.780G>A | p.Lys260= | synonymous_variant | 4/15 | 5 | ENSP00000263946 | |||
PKP1 | ENST00000352845.3 | c.780G>A | p.Lys260= | synonymous_variant | 4/14 | 5 | ENSP00000295597 | |||
PKP1 | ENST00000475988.1 | n.122G>A | non_coding_transcript_exon_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0295 AC: 4483AN: 152200Hom.: 194 Cov.: 33
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GnomAD4 exome AF: 0.00454 AC: 6634AN: 1461272Hom.: 213 Cov.: 33 AF XY: 0.00431 AC XY: 3130AN XY: 726836
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GnomAD4 genome AF: 0.0295 AC: 4491AN: 152318Hom.: 194 Cov.: 33 AF XY: 0.0284 AC XY: 2115AN XY: 74484
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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 submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
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Prediction
BayesDel_noAF
Benign
CADD
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at