Variant 15-50439193-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005154.5(USP8):c.104+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,365,970 control chromosomes in the GnomAD database, including 20,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2121 hom., cov: 32)

Exomes 𝑓: 0.17 ( 18539 hom. )

Consequence

USP8
NM_005154.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0130

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 15-50439193-C-T is Benign according to our data. Variant chr15-50439193-C-T is described in ClinVar as [Benign]. Clinvar id is 1600612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
USP8	NM_005154.5 linkuse as main transcript	c.104+16C>T	intron_variant	ENST00000307179.9
USP8	NM_001128610.3 linkuse as main transcript	c.104+16C>T	intron_variant
USP8	NM_001283049.2 linkuse as main transcript	c.104+16C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP8	ENST00000307179.9 linkuse as main transcript	c.104+16C>T		intron_variant		1	NM_005154.5	P1	P40818-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22885

AN:

151988

Hom.:

2117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0973

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.00288

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.0799

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.188

GnomAD3 exomes

AF:

0.171

AC:

26317

AN:

154088

Hom.:

2747

AF XY:

0.175

AC XY:

14912

AN XY:

85402

show subpopulations

Gnomad AFR exome

AF:

0.0954

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.00235

Gnomad SAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.0860

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.167

AC:

203041

AN:

1213864

Hom.:

18539

Cov.:

AF XY:

0.169

AC XY:

101019

AN XY:

598878

show subpopulations

Gnomad4 AFR exome

AF:

0.0958

Gnomad4 AMR exome

AF:

0.314

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.000934

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.0890

Gnomad4 NFE exome

AF:

0.170

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.151

AC:

22901

AN:

152106

Hom.:

2121

Cov.:

AF XY:

0.149

AC XY:

11063

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0975

Gnomad4 AMR

AF:

0.272

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.0799

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.181

Hom.:

2792

Bravo

AF:

0.164

Asia WGS

AF:

0.0990

AC:

344

AN:

3474

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 31, 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

-0.77

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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