rs781396270

Variant names:

• chr11-396618-G-C
• rs781396270
• NM_007183.4:c.243G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-396618-G-C
• chr11-396618-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007183.4(PKP3):​c.243G>C​(p.Arg81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,606,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: PKP3 NM_007183.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.796
• Publications: 0 publications found

Genes affected

PKP3 (HGNC:9025): (plakophilin 3) 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 act in cellular desmosome-dependent adhesion and signaling pathways. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096506774).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007183.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP3	NM_007183.4	MANE Select	c.243G>C	p.Arg81Ser	missense	Exon 2 of 13	NP_009114.1	Q9Y446-1
	PKP3	NM_001303029.2		c.288G>C	p.Arg96Ser	missense	Exon 3 of 14	NP_001289958.1	Q9Y446-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP3	ENST00000331563.7	TSL:1 MANE Select	c.243G>C	p.Arg81Ser	missense	Exon 2 of 13	ENSP00000331678.2	Q9Y446-1
	PKP3	ENST00000534401.6	TSL:3	c.288G>C	p.Arg96Ser	missense	Exon 3 of 14	ENSP00000434517.3	Q9Y446-2
	PKP3	ENST00000895790.1		c.243G>C	p.Arg81Ser	missense	Exon 2 of 13	ENSP00000565849.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152216 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000203 AC: 5 AN: 245968 AF XY: 0.0000225

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000588

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000268 AC: 39 AN: 1454674 Hom.: 0 Cov.: 31 AF XY: 0.0000249 AC XY: 18 AN XY: 723286

African (AFR) AF: 0.0000300 AC: 1 AN: 33328

American (AMR) AF: 0.0000679 AC: 3 AN: 44192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4866

European-Non Finnish (NFE) AF: 0.0000316 AC: 35 AN: 1108998

Other (OTH) AF: 0.00 AC: 0 AN: 60028

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152216 Hom.: 0 Cov.: 34 AF XY: 0.0000672 AC XY: 5 AN XY: 74356

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000566 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.00000826 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	2.5
DANN	Benign	0.96
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.80
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.12	N
REVEL	Uncertain	0.32
Sift	Benign	0.32	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.45
MutPred		0.31		Loss of MoRF binding (P = 0.0076)
MVP		0.45
MPC		0.080
ClinPred		0.060	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.091
gMVP		0.32
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs781396270; hg19: chr11-396618;