Variant 16-4883408-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002705.5(PPL):c.5247G>C(p.Ala1749=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,614,144 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 16 hom. )

Consequence

PPL
NM_002705.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.85

Variant links:

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]

PPL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 16-4883408-C-G is Benign according to our data. Variant chr16-4883408-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2646162.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.85 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PPL	NM_002705.5 linkuse as main transcript	c.5247G>C	p.Ala1749=	synonymous_variant	22/22	ENST00000345988.7	NP_002696.4
PPL	XM_017023374.3 linkuse as main transcript	c.5334G>C	p.Ala1778=	synonymous_variant	22/22		XP_016878863.1
PPL	XM_017023375.3 linkuse as main transcript	c.5295G>C	p.Ala1765=	synonymous_variant	22/22		XP_016878864.1
PPL	XM_006720902.5 linkuse as main transcript	c.5286G>C	p.Ala1762=	synonymous_variant	22/22		XP_006720965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPL	ENST00000345988.7 linkuse as main transcript	c.5247G>C	p.Ala1749=	synonymous_variant	22/22	1	NM_002705.5	ENSP00000340510	P3
PPL	ENST00000590782.6 linkuse as main transcript	c.5241G>C	p.Ala1747=	synonymous_variant	22/22	5		ENSP00000465640	A1

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00317

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00226

AC:

569

AN:

251354

Hom.:

AF XY:

0.00238

AC XY:

323

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.00368

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00305

AC:

4455

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

2171

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000870

Gnomad4 FIN exome

AF:

0.00234

Gnomad4 NFE exome

AF:

0.00353

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00217

AC:

330

AN:

152314

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00277

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

PPL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.074

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over