rs373691974

Variant names:

• chr11-396874-G-A
• rs373691974
• NM_007183.4:c.373G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-396874-G-A
• chr11-396874-G-C
• chr11-396874-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007183.4(PKP3):​c.373G>A​(p.Val125Met) variant causes a missense change. The variant allele was found at a frequency of 0.000055 in 1,599,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: PKP3 NM_007183.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14520547).

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.373G>A	p.Val125Met	missense	Exon 3 of 13	NP_009114.1	Q9Y446-1
	PKP3	NM_001303029.2		c.418G>A	p.Val140Met	missense	Exon 4 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.373G>A	p.Val125Met	missense	Exon 3 of 13	ENSP00000331678.2	Q9Y446-1
	PKP3	ENST00000527442.6	TSL:3	c.-96G>A		5_prime_UTR_premature_start_codon_gain	Exon 4 of 14	ENSP00000435522.2	E9PRW6
	PKP3	ENST00000528036.6	TSL:2	c.-96G>A		5_prime_UTR_premature_start_codon_gain	Exon 4 of 14	ENSP00000434110.2	E9PRW6

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152232 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000501 AC: 11 AN: 219656 AF XY: 0.0000495

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000519

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000207

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000546 AC: 79 AN: 1447392 Hom.: 0 Cov.: 34 AF XY: 0.0000556 AC XY: 40 AN XY: 719630

African (AFR) AF: 0.00 AC: 0 AN: 33284

American (AMR) AF: 0.00 AC: 0 AN: 43940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25902

East Asian (EAS) AF: 0.000407 AC: 16 AN: 39320

South Asian (SAS) AF: 0.00 AC: 0 AN: 84928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.0000541 AC: 60 AN: 1108268

Other (OTH) AF: 0.0000500 AC: 3 AN: 59956

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152350 Hom.: 0 Cov.: 34 AF XY: 0.0000671 AC XY: 5 AN XY: 74502

African (AFR) AF: 0.0000481 AC: 2 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000491

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000231 AC: 1

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.0000333 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.032
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.00060	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.81	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.42
MVP		0.69
MPC		0.38
ClinPred		0.21	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.056
gMVP		0.51
Mutation Taster		=85/15	polymorphism

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: rs373691974; hg19: chr11-396874;