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GeneBe

16-4885145-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002705.5(PPL):c.3510G>A(p.Val1170=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,822 control chromosomes in the GnomAD database, including 80,409 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 0.31 ( 7748 hom., cov: 31)
Exomes 𝑓: 0.31 ( 72661 hom. )

Consequence

PPL
NM_002705.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.246
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.246 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPLNM_002705.5 linkuse as main transcriptc.3510G>A p.Val1170= synonymous_variant 22/22 ENST00000345988.7
PPLXM_017023374.3 linkuse as main transcriptc.3597G>A p.Val1199= synonymous_variant 22/22
PPLXM_017023375.3 linkuse as main transcriptc.3558G>A p.Val1186= synonymous_variant 22/22
PPLXM_006720902.5 linkuse as main transcriptc.3549G>A p.Val1183= synonymous_variant 22/22

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPLENST00000345988.7 linkuse as main transcriptc.3510G>A p.Val1170= synonymous_variant 22/221 NM_002705.5 P3
PPLENST00000590782.6 linkuse as main transcriptc.3504G>A p.Val1168= synonymous_variant 22/225 A1
PPLENST00000592772.1 linkuse as main transcriptc.1773G>A p.Val591= synonymous_variant 10/105

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.315
AC:
47792
AN:
151944
Hom.:
7726
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.338
Gnomad AMI
AF:
0.154
Gnomad AMR
AF:
0.342
Gnomad ASJ
AF:
0.435
Gnomad EAS
AF:
0.304
Gnomad SAS
AF:
0.474
Gnomad FIN
AF:
0.243
Gnomad MID
AF:
0.421
Gnomad NFE
AF:
0.289
Gnomad OTH
AF:
0.346
GnomAD3 exomes
AF:
0.334
AC:
83999
AN:
251340
Hom.:
14806
AF XY:
0.335
AC XY:
45547
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.338
Gnomad AMR exome
AF:
0.386
Gnomad ASJ exome
AF:
0.444
Gnomad EAS exome
AF:
0.295
Gnomad SAS exome
AF:
0.466
Gnomad FIN exome
AF:
0.256
Gnomad NFE exome
AF:
0.294
Gnomad OTH exome
AF:
0.330
GnomAD4 exome
AF:
0.311
AC:
453900
AN:
1461760
Hom.:
72661
Cov.:
85
AF XY:
0.314
AC XY:
228572
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.342
Gnomad4 AMR exome
AF:
0.384
Gnomad4 ASJ exome
AF:
0.433
Gnomad4 EAS exome
AF:
0.315
Gnomad4 SAS exome
AF:
0.458
Gnomad4 FIN exome
AF:
0.259
Gnomad4 NFE exome
AF:
0.294
Gnomad4 OTH exome
AF:
0.329
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.315
AC:
47855
AN:
152062
Hom.:
7748
Cov.:
31
AF XY:
0.317
AC XY:
23562
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.339
Gnomad4 AMR
AF:
0.343
Gnomad4 ASJ
AF:
0.435
Gnomad4 EAS
AF:
0.303
Gnomad4 SAS
AF:
0.473
Gnomad4 FIN
AF:
0.243
Gnomad4 NFE
AF:
0.289
Gnomad4 OTH
AF:
0.346
Alfa
AF:
0.309
Hom.:
11995
Bravo
AF:
0.322
Asia WGS
AF:
0.422
AC:
1465
AN:
3478
EpiCase
AF:
0.302
EpiControl
AF:
0.314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
3.5
Dann
Benign
0.90

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.

Other links and lift over

dbSNP: rs1049206; hg19: chr16-4935146; COSMIC: COSV52165750; COSMIC: COSV52165750; API