11-396821-G-C

Variant names:

• chr11-396821-G-C
• rs544269907
• NM_007183.4:c.320G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007183.4(PKP3):​c.320G>C​(p.Arg107Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,435,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PKP3 NM_007183.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29423094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP3	NM_007183.4	c.320G>C	p.Arg107Pro	missense_variant	Exon 3 of 13	ENST00000331563.7	NP_009114.1
PKP3	NM_001303029.2	c.365G>C	p.Arg122Pro	missense_variant	Exon 4 of 14		NP_001289958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKP3	ENST00000331563.7	c.320G>C	p.Arg107Pro	missense_variant	Exon 3 of 13	1	NM_007183.4	ENSP00000331678.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000479 AC: 1 AN: 208878 Hom.: 0 AF XY: 0.00000863 AC XY: 1 AN XY: 115906

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000368

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000418 AC: 6 AN: 1435068 Hom.: 0 Cov.: 34 AF XY: 0.00000842 AC XY: 6 AN XY: 712638

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000720

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	.;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.69	.;N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.010	.;N;D
REVEL	Uncertain	0.51
Sift	Benign	0.30	.;T;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.41	.;B;.
Vest4		0.34
MutPred		0.37		.;Loss of MoRF binding (P = 0.0093);.;
MVP		0.76
MPC		0.20
ClinPred		0.37	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs544269907; hg19: chr11-396821;