chr16-4883408-C-G
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_002705.5(PPL):āc.5247G>Cā(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 (ā ).
Frequency
Genomes: š 0.0022 ( 3 hom., cov: 32)
Exomes š: 0.0030 ( 16 hom. )
Consequence
PPL
NM_002705.5 synonymous
NM_002705.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.85
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 -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 | UniProt |
---|---|---|---|---|---|---|---|---|
PPL | NM_002705.5 | c.5247G>C | p.Ala1749= | synonymous_variant | 22/22 | ENST00000345988.7 | NP_002696.4 | |
PPL | XM_017023374.3 | c.5334G>C | p.Ala1778= | synonymous_variant | 22/22 | XP_016878863.1 | ||
PPL | XM_017023375.3 | c.5295G>C | p.Ala1765= | synonymous_variant | 22/22 | XP_016878864.1 | ||
PPL | XM_006720902.5 | 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 | c.5247G>C | p.Ala1749= | synonymous_variant | 22/22 | 1 | NM_002705.5 | ENSP00000340510 | P3 | |
PPL | ENST00000590782.6 | c.5241G>C | p.Ala1747= | synonymous_variant | 22/22 | 5 | ENSP00000465640 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00217 AC: 330AN: 152196Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00226 AC: 569AN: 251354Hom.: 4 AF XY: 0.00238 AC XY: 323AN XY: 135862
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GnomAD4 exome AF: 0.00305 AC: 4455AN: 1461830Hom.: 16 Cov.: 34 AF XY: 0.00299 AC XY: 2171AN XY: 727222
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GnomAD4 genome AF: 0.00217 AC: 330AN: 152314Hom.: 3 Cov.: 32 AF XY: 0.00211 AC XY: 157AN XY: 74496
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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
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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