Variant 15-50449385-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005154.5(USP8):c.250-15T>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 0.000519 in 1,538,486 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 1 hom. )

Consequence

USP8
NM_005154.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.54

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 15-50449385-T-C is Benign according to our data. Variant chr15-50449385-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1629850.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
USP8	NM_005154.5 linkuse as main transcript	c.250-15T>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000307179.9	NP_005145.3
USP8	NM_001128610.3 linkuse as main transcript	c.250-15T>C	splice_polypyrimidine_tract_variant, intron_variant		NP_001122082.1
USP8	NM_001283049.2 linkuse as main transcript	c.105-9615T>C	intron_variant		NP_001269978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP8	ENST00000307179.9 linkuse as main transcript	c.250-15T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005154.5	ENSP00000302239	P1	P40818-1

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000280

AC:

AN:

217616

Hom.:

AF XY:

0.000270

AC XY:

AN XY:

118486

show subpopulations

Gnomad AFR exome

AF:

0.0000690

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000286

Gnomad NFE exome

AF:

0.000446

Gnomad OTH exome

AF:

0.000388

GnomAD4 exome

AF:

0.000530

AC:

735

AN:

1386168

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

333

AN XY:

689624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000325

Gnomad4 AMR exome

AF:

0.000193

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000213

Gnomad4 NFE exome

AF:

0.000649

Gnomad4 OTH exome

AF:

0.000403

GnomAD4 genome

AF:

0.000414

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000684

Hom.:

Bravo

AF:

0.000340

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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