16-4882559-T-G

Position:

• chr16-4882559-T-G

Variant summary

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

The NM_002705.5(PPL):​c.*825A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,892 control chromosomes in the GnomAD database, including 23,657 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 0.53 (23655 hom., cov: 31)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: PPL NM_002705.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPL	NM_002705.5	c.*825A>C		3_prime_UTR_variant	22/22	ENST00000345988.7	NP_002696.4
PPL	XM_006720902.5	c.*825A>C		3_prime_UTR_variant	22/22		XP_006720965.1
PPL	XM_017023374.3	c.*825A>C		3_prime_UTR_variant	22/22		XP_016878863.1
PPL	XM_017023375.3	c.*825A>C		3_prime_UTR_variant	22/22		XP_016878864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPL	ENST00000345988.7	c.*825A>C		3_prime_UTR_variant	22/22	1	NM_002705.5	ENSP00000340510	P3

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80891 AN: 151712 Hom.: 23603 Cov.: 31

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.161 AC: 10 AN: 62 Hom.: 2 Cov.: 0 AF XY: 0.158 AC XY: 6 AN XY: 38

Gnomad4 FIN exome AF: 0.0800

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.533 AC: 80998 AN: 151830 Hom.: 23655 Cov.: 31 AF XY: 0.530 AC XY: 39323 AN XY: 74186

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.521

Alfa AF: 0.473 Hom.: 6939

Bravo AF: 0.556

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs7214; hg19: chr16-4932560;