11-396618-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007183.4(PKP3):​c.243G>A​(p.Arg81Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,674 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: 6.9e-7 (0 hom.)
• Consequence: PKP3 NM_007183.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.796 with no splicing effect.

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>A	p.Arg81Arg	synonymous	Exon 2 of 13	NP_009114.1	Q9Y446-1
	PKP3	NM_001303029.2		c.288G>A	p.Arg96Arg	synonymous	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>A	p.Arg81Arg	synonymous	Exon 2 of 13	ENSP00000331678.2	Q9Y446-1
	PKP3	ENST00000534401.6	TSL:3	c.288G>A	p.Arg96Arg	synonymous	Exon 3 of 14	ENSP00000434517.3	Q9Y446-2
	PKP3	ENST00000895790.1		c.243G>A	p.Arg81Arg	synonymous	Exon 2 of 13	ENSP00000565849.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245968 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000905

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454674 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723286

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 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: 9.02e-7 AC: 1 AN: 1108998

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.86
PhyloP100		-0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;