chr15-50497080-T-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_005154.5(USP8):c.2896-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,587,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
USP8
NM_005154.5 splice_polypyrimidine_tract, intron
NM_005154.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00002627
2
Clinical Significance
Conservation
PhyloP100: 0.716
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 15-50497080-T-C is Benign according to our data. Variant chr15-50497080-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 704486.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP8 | NM_005154.5 | c.2896-9T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000307179.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP8 | ENST00000307179.9 | c.2896-9T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005154.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000190 AC: 29AN: 152264Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000220 AC: 49AN: 222404Hom.: 0 AF XY: 0.000240 AC XY: 29AN XY: 120910
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GnomAD4 exome AF: 0.000247 AC: 355AN: 1435178Hom.: 0 Cov.: 30 AF XY: 0.000262 AC XY: 187AN XY: 713664
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GnomAD4 genome ? AF: 0.000190 AC: 29AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74384
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at