rs11857513
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The ENST00000307179.9(USP8):c.3033G>A(p.Leu1011=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,602,510 control chromosomes in the GnomAD database, including 1,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 70 hom., cov: 33)
Exomes 𝑓: 0.031 ( 1010 hom. )
Consequence
USP8
ENST00000307179.9 synonymous
ENST00000307179.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.84
Genes affected
USP8 (HGNC:12631): (ubiquitin specific peptidase 8) This gene encodes a protein that belongs to the ubiquitin-specific processing protease family of proteins. The encoded protein is thought to regulate the morphology of the endosome by ubiquitination of proteins on this organelle and is involved in cargo sorting and membrane trafficking at the early endosome stage. This protein is required for the cell to enter the S phase of the cell cycle and also functions as a positive regulator in the Hedgehog signaling pathway in development. Pseudogenes of this gene are present on chromosomes 2 and 6. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
USP50 (HGNC:20079): (ubiquitin specific peptidase 50) Enables ubiquitin-like protein-specific protease activity. Acts upstream of or within several processes, including nuclear speck organization; positive regulation of NLRP3 inflammasome complex assembly; and positive regulation of macromolecule metabolic process. Predicted to be active in several cellular components, including dendritic spine; midbody; and postsynaptic density. Predicted to be extrinsic component of endosome membrane and extrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP6
Variant 15-50497226-G-A is Benign according to our data. Variant chr15-50497226-G-A is described in ClinVar as [Benign]. Clinvar id is 458316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.84 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USP8 | NM_005154.5 | c.3033G>A | p.Leu1011= | synonymous_variant | 18/20 | ENST00000307179.9 | NP_005145.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USP8 | ENST00000307179.9 | c.3033G>A | p.Leu1011= | synonymous_variant | 18/20 | 1 | NM_005154.5 | ENSP00000302239 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0244 AC: 3711AN: 152186Hom.: 72 Cov.: 33
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GnomAD3 exomes AF: 0.0311 AC: 7422AN: 238920Hom.: 155 AF XY: 0.0317 AC XY: 4093AN XY: 129250
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GnomAD4 exome AF: 0.0309 AC: 44746AN: 1450206Hom.: 1010 Cov.: 30 AF XY: 0.0314 AC XY: 22666AN XY: 721240
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GnomAD4 genome AF: 0.0243 AC: 3706AN: 152304Hom.: 70 Cov.: 33 AF XY: 0.0254 AC XY: 1895AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at