rs753607257

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-394354-C-A
• chr11-394354-C-G
• chr11-394354-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007183.4(PKP3):​c.62C>A​(p.Ala21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,360,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A21V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP3	NM_007183.4	c.62C>A	p.Ala21Glu	missense_variant	Exon 1 of 13	ENST00000331563.7	NP_009114.1
PKP3	NM_001303029.2	c.107C>A	p.Ala36Glu	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>A	p.Ala21Glu	missense_variant	Exon 1 of 13	1	NM_007183.4	ENSP00000331678.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1360106 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 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: 0.0000129

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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.75	T;T
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Benign	1.7	.;L
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.2	.;N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0020	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.61
MutPred		0.39		.;Gain of solvent accessibility (P = 0.0145);
MVP		0.92
MPC		0.33
ClinPred		0.94	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.64
gMVP		0.73

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;