USP8 p.Leu1011Leu

Variant names:

• chr15-50497223-T-T
• ENST00000307179.9:c.

Your query was ambiguous. Multiple possible variants found:

• chr15-50497224--
• chr15-50497224-C-T
• chr15-50497226-G-T
• chr15-50497226-G-C
• chr15-50497226-G-A
• chr15-50497224-CTG-TTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000307179.9(USP8):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: USP8 ENST00000307179.9 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000307179.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP8	ENST00000307179.9	TSL:1 MANE Select	c.		exon_region	Exon 18 of 20	ENSP00000302239.4	P40818-1
	USP8	ENST00000396444.7	TSL:1	c.		exon_region	Exon 18 of 20	ENSP00000379721.3	P40818-1
	USP8	ENST00000956759.1		c.		exon_region	Exon 19 of 21	ENSP00000626818.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-50789420;