chr16-4883623-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000345988.7(PPL):c.5032G>C(p.Gly1678Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PPL
ENST00000345988.7 missense
ENST00000345988.7 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 5.05
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.841
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPL | NM_002705.5 | c.5032G>C | p.Gly1678Arg | missense_variant | 22/22 | ENST00000345988.7 | NP_002696.4 | |
PPL | XM_017023374.3 | c.5119G>C | p.Gly1707Arg | missense_variant | 22/22 | XP_016878863.1 | ||
PPL | XM_017023375.3 | c.5080G>C | p.Gly1694Arg | missense_variant | 22/22 | XP_016878864.1 | ||
PPL | XM_006720902.5 | c.5071G>C | p.Gly1691Arg | missense_variant | 22/22 | XP_006720965.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPL | ENST00000345988.7 | c.5032G>C | p.Gly1678Arg | missense_variant | 22/22 | 1 | NM_002705.5 | ENSP00000340510 | P3 | |
PPL | ENST00000590782.6 | c.5026G>C | p.Gly1676Arg | missense_variant | 22/22 | 5 | ENSP00000465640 | A1 | ||
PPL | ENST00000592772.1 | c.3295G>C | p.Gly1099Arg | missense_variant | 10/10 | 5 | ENSP00000467699 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 28, 2024 | The c.5032G>C (p.G1678R) alteration is located in exon 22 (coding exon 22) of the PPL gene. This alteration results from a G to C substitution at nucleotide position 5032, causing the glycine (G) at amino acid position 1678 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Pathogenic
D;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.
Sift4G
Benign
T;T;.
Polyphen
P;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0422);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.