ENST00000592772.1:c.-92+9185T>C

Variant names:

• chr16-4951379-A-G
• rs9635542
• ENST00000592772.1:c.-92+9185T>C

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPL	ENST00000592772.1	c.-92+9185T>C		intron_variant	Intron 1 of 9	5		ENSP00000467699.1

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;