Variant rs11857513 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005154.5(USP8):c.3033G>A(p.Leu1011Leu) 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
NM_005154.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.84

Variant links:

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]

USP8 links:

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]

USP50 links:

USP8 (HGNC:):

USP8 links:

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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 linkuse as main transcript	c.3033G>A	p.Leu1011Leu	synonymous_variant	18/20	ENST00000307179.9	NP_005145.3	P40818-1A0A024R5S4A8K8N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP8	ENST00000307179.9 linkuse as main transcript	c.3033G>A	p.Leu1011Leu	synonymous_variant	18/20	1	NM_005154.5	ENSP00000302239.4		P40818-1

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3711

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00714

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.0871

Gnomad SAS

AF:

0.0524

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0311

AC:

7422

AN:

238920

Hom.:

155

AF XY:

0.0317

AC XY:

4093

AN XY:

129250

show subpopulations

Gnomad AFR exome

AF:

0.00542

Gnomad AMR exome

AF:

0.0249

Gnomad ASJ exome

AF:

0.0171

Gnomad EAS exome

AF:

0.0632

Gnomad SAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.0284

Gnomad OTH exome

AF:

0.0269

GnomAD4 exome

AF:

0.0309

AC:

44746

AN:

1450206

Hom.:

1010

Cov.:

AF XY:

0.0314

AC XY:

22666

AN XY:

721240

show subpopulations

Gnomad4 AFR exome

AF:

0.00482

Gnomad4 AMR exome

AF:

0.0244

Gnomad4 ASJ exome

AF:

0.0187

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.0470

Gnomad4 FIN exome

AF:

0.0267

Gnomad4 NFE exome

AF:

0.0279

Gnomad4 OTH exome

AF:

0.0309

GnomAD4 genome

AF:

0.0243

AC:

3706

AN:

152304

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1895

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00712

Gnomad4 AMR

AF:

0.0215

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.0869

Gnomad4 SAS

AF:

0.0514

Gnomad4 FIN

AF:

0.0276

Gnomad4 NFE

AF:

0.0289

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0251

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.0910

AC:

316

AN:

3478

EpiCase

AF:

0.0272

EpiControl

AF:

0.0294

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

8.6

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over