chr16-4885145-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
NM_002705.5 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.246
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
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP7
?
Synonymous conserved (PhyloP=-0.246 with no splicing effect.
BA1
?
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 |
---|---|---|---|---|---|---|---|
PPL | NM_002705.5 | c.3510G>A | p.Val1170= | synonymous_variant | 22/22 | ENST00000345988.7 | |
PPL | XM_017023374.3 | c.3597G>A | p.Val1199= | synonymous_variant | 22/22 | ||
PPL | XM_017023375.3 | c.3558G>A | p.Val1186= | synonymous_variant | 22/22 | ||
PPL | XM_006720902.5 | c.3549G>A | p.Val1183= | synonymous_variant | 22/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPL | ENST00000345988.7 | c.3510G>A | p.Val1170= | synonymous_variant | 22/22 | 1 | NM_002705.5 | P3 | |
PPL | ENST00000590782.6 | c.3504G>A | p.Val1168= | synonymous_variant | 22/22 | 5 | A1 | ||
PPL | ENST00000592772.1 | c.1773G>A | p.Val591= | synonymous_variant | 10/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.315 AC: 47792AN: 151944Hom.: 7726 Cov.: 31
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GnomAD3 exomes AF: 0.334 AC: 83999AN: 251340Hom.: 14806 AF XY: 0.335 AC XY: 45547AN XY: 135864
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GnomAD4 exome AF: 0.311 AC: 453900AN: 1461760Hom.: 72661 Cov.: 85 AF XY: 0.314 AC XY: 228572AN XY: 727192
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GnomAD4 genome ? AF: 0.315 AC: 47855AN: 152062Hom.: 7748 Cov.: 31 AF XY: 0.317 AC XY: 23562AN XY: 74328
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at