1-201316631-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005337.3(PKP1):​c.780G>C​(p.Lys260Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K260M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PKP1
NM_001005337.3 missense

Scores

1
7

Clinical Significance

Not reported in ClinVar

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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12784159).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKP1NM_001005337.3 linkc.780G>C p.Lys260Asn missense_variant Exon 4 of 14 ENST00000367324.8 NP_001005337.1 Q13835-2A0A024R952
PKP1NM_000299.4 linkc.780G>C p.Lys260Asn missense_variant Exon 4 of 15 NP_000290.2 Q13835-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKP1ENST00000367324.8 linkc.780G>C p.Lys260Asn missense_variant Exon 4 of 14 1 NM_001005337.3 ENSP00000356293.4 Q13835-2
PKP1ENST00000263946.7 linkc.780G>C p.Lys260Asn missense_variant Exon 4 of 15 5 ENSP00000263946.3 Q13835-1
PKP1ENST00000352845.3 linkc.780G>C p.Lys260Asn missense_variant Exon 4 of 14 5 ENSP00000295597.3 Q13835-1
PKP1ENST00000475988.1 linkn.122G>C non_coding_transcript_exon_variant Exon 2 of 5 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.56
BayesDel_noAF
Benign
-0.65
CADD
Benign
20
DEOGEN2
Benign
0.017
.;T;T
LIST_S2
Benign
0.82
T;T;.
MetaRNN
Benign
0.13
T;T;T
PROVEAN
Benign
-0.68
N;N;N
Sift
Benign
0.30
T;T;T
Sift4G
Benign
0.47
T;T;T
Vest4
0.18
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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