rs149396982

Variant names:

• chr11-396686-C-G
• NM_007183.4:c.311C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-396686-C-G
• chr11-396686-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007183.4(PKP3):​c.311C>G​(p.Ser104Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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 missense, splice_region
• Scores: Splicing: ADA: 0.006367
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2846787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKP3	NM_007183.4	c.311C>G	p.Ser104Trp	missense_variant, splice_region_variant	Exon 2 of 13	ENST00000331563.7	NP_009114.1
PKP3	NM_001303029.2	c.356C>G	p.Ser119Trp	missense_variant, splice_region_variant	Exon 3 of 14		NP_001289958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKP3	ENST00000331563.7	c.311C>G	p.Ser104Trp	missense_variant, splice_region_variant	Exon 2 of 13	1	NM_007183.4	ENSP00000331678.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457386 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724838

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: 0.0000117

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	Benign	0.17
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	.;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.81	.;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	.;N;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0080	.;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.99	.;D;.
Vest4		0.59
MutPred		0.40		.;Loss of phosphorylation at S104 (P = 0.0269);.;
MVP		0.77
MPC		0.30
ClinPred		0.62	D
GERP RS		1.2
Varity_R		0.099
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0064
dbscSNV1_RF	Benign	0.17
SpliceAI score (max)		0.090		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: chr11-396686;