chr15-50497248-GTCC-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_005154.5(USP8):c.3038+22_3038+24del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,592,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
USP8
NM_005154.5 intron
NM_005154.5 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.93
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 Likely_benign. Variant got -6 ACMG points.
BP6
?
Variant 15-50497248-GTCC-G is Benign according to our data. Variant chr15-50497248-GTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2989900.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USP8 | NM_005154.5 | c.3038+22_3038+24del | intron_variant | ENST00000307179.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USP8 | ENST00000307179.9 | c.3038+22_3038+24del | intron_variant | 1 | NM_005154.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152148Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000704 AC: 16AN: 227118Hom.: 0 AF XY: 0.0000812 AC XY: 10AN XY: 123144
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GnomAD4 exome AF: 0.0000201 AC: 29AN: 1439774Hom.: 0 AF XY: 0.0000223 AC XY: 16AN XY: 715902
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74444
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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 | Aug 10, 2023 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at