rs9635542

Positions:

• chr16-4951379-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000592772.1(PPL):​c.-92+9185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 151,542 control chromosomes in the GnomAD database, including 1,452 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 0.11 (1452 hom., cov: 30)
• Consequence: PPL ENST00000592772.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

Genes affected

PPL (HGNC:9273): (periplakin) The protein encoded by this gene is a component of desmosomes and of the epidermal cornified envelope in keratinocytes. The N-terminal domain of this protein interacts with the plasma membrane and its C-terminus interacts with intermediate filaments. Through its rod domain, this protein forms complexes with envoplakin. This protein may serve as a link between the cornified envelope and desmosomes as well as intermediate filaments. AKT1/PKB, a protein kinase mediating a variety of cell growth and survival signaling processes, is reported to interact with this protein, suggesting a possible role for this protein as a localization signal in AKT1-mediated signaling. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPL	ENST00000592772.1	c.-92+9185T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17347 AN: 151432 Hom.: 1448 Cov.: 30

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.115 AC: 17367 AN: 151542 Hom.: 1452 Cov.: 30 AF XY: 0.121 AC XY: 8936 AN XY: 73984

Gnomad4 AFR AF: 0.0666

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0870

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.119

Alfa AF: 0.112 Hom.: 2327

Bravo AF: 0.110

Asia WGS AF: 0.376 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9635542; hg19: chr16-5001380;