NM_003628.6:c.1909+3805G>A

Variant names:

• chr2-158646504-G-A
• rs929390
• NM_003628.6:c.1909+3805G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003628.6(PKP4):​c.1909+3805G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,984 control chromosomes in the GnomAD database, including 16,377 homozygotes. 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: 𝑓 0.45 (16377 hom., cov: 32)
• Consequence: PKP4 NM_003628.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 9 publications found

Genes affected

PKP4 (HGNC:9026): (plakophilin 4) Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003628.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP4	NM_003628.6	MANE Select	c.1909+3805G>A		intron	N/A	NP_003619.2
	PKP4	NM_001377218.1		c.1909+3805G>A		intron	N/A	NP_001364147.1
	PKP4	NM_001304969.3		c.1906+3805G>A		intron	N/A	NP_001291898.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP4	ENST00000389759.8	TSL:1 MANE Select	c.1909+3805G>A		intron	N/A	ENSP00000374409.3
	PKP4	ENST00000389757.7	TSL:1	c.1909+3805G>A		intron	N/A	ENSP00000374407.3
	PKP4	ENST00000426248.7	TSL:1	n.*1178+3805G>A		intron	N/A	ENSP00000396827.2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67751 AN: 151868 Hom.: 16359 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.434

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67793 AN: 151984 Hom.: 16377 Cov.: 32 AF XY: 0.450 AC XY: 33386 AN XY: 74260

African (AFR) AF: 0.259 AC: 10731 AN: 41456

American (AMR) AF: 0.584 AC: 8918 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1441 AN: 3466

East Asian (EAS) AF: 0.596 AC: 3081 AN: 5168

South Asian (SAS) AF: 0.664 AC: 3190 AN: 4802

European-Finnish (FIN) AF: 0.449 AC: 4736 AN: 10552

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34276 AN: 67958

Other (OTH) AF: 0.435 AC: 918 AN: 2108

Alfa AF: 0.498 Hom.: 12000

Bravo AF: 0.445

Asia WGS AF: 0.584 AC: 2029 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.030
DANN	Benign	0.53
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs929390; hg19: chr2-159503016;