11-394354-C-G

Variant names:

• chr11-394354-C-G
• NM_007183.4:c.62C>G

Variant summary

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

The NM_007183.4(PKP3):​c.62C>G​(p.Ala21Gly) 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. 12/21 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKP3 NM_007183.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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=0.32358786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP3	NM_007183.4	c.62C>G	p.Ala21Gly	missense_variant	Exon 1 of 13	ENST00000331563.7	NP_009114.1
PKP3	NM_001303029.2	c.107C>G	p.Ala36Gly	missense_variant	Exon 2 of 14		NP_001289958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKP3	ENST00000331563.7	c.62C>G	p.Ala21Gly	missense_variant	Exon 1 of 13	1	NM_007183.4	ENSP00000331678.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1360106 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 671298

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: 0.00

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	0.30
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.058
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.76	T;T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.5	.;N
REVEL	Benign	0.27
Sift	Uncertain	0.0090	.;D
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.26	.;B
Vest4		0.30
MutPred		0.29		.;Gain of relative solvent accessibility (P = 0.0023);
MVP		0.78
MPC		0.26
ClinPred		0.86	D
GERP RS		3.1
Varity_R		0.33
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-394354;