NM_007183.4:c.233-62G>C

Variant names:

• chr11-396546-G-C
• rs7105848
• NM_007183.4:c.233-62G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007183.4(PKP3):​c.233-62G>C variant causes a intron 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.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PKP3 NM_007183.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• Publications: 14 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP3	NM_007183.4	c.233-62G>C		intron_variant	Intron 1 of 12	ENST00000331563.7	NP_009114.1
PKP3	NM_001303029.2	c.278-62G>C		intron_variant	Intron 2 of 13		NP_001289958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKP3	ENST00000331563.7	c.233-62G>C		intron_variant	Intron 1 of 12	1	NM_007183.4	ENSP00000331678.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 13

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.63
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7105848; hg19: chr11-396546;