Variant chr15-50484328-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005154.5(USP8):c.1857T>C(p.Phe619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,611,854 control chromosomes in the GnomAD database, including 3,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 1336 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1806 hom. )

Consequence

USP8
NM_005154.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.15

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 15-50484328-T-C is Benign according to our data. Variant chr15-50484328-T-C is described in ClinVar as [Benign]. Clinvar id is 458314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USP8	NM_005154.5 linkuse as main transcript	c.1857T>C	p.Phe619=	synonymous_variant	12/20	ENST00000307179.9
USP8	NM_001128610.3 linkuse as main transcript	c.1857T>C	p.Phe619=	synonymous_variant	12/20
USP8	NM_001283049.2 linkuse as main transcript	c.1572+2263T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP8	ENST00000307179.9 linkuse as main transcript	c.1857T>C	p.Phe619=	synonymous_variant	12/20	1	NM_005154.5	P1	P40818-1
USP8	ENST00000396444.7 linkuse as main transcript	c.1857T>C	p.Phe619=	synonymous_variant	12/20	1		P1	P40818-1
USP8	ENST00000425032.7 linkuse as main transcript	c.1572+2263T>C		intron_variant		2			P40818-2

Frequencies

GnomAD3 genomes

AF:

0.0898

AC:

13656

AN:

152056

Hom.:

1335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0559

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.0189

Gnomad SAS

AF:

0.0313

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0285

Gnomad OTH

AF:

0.0704

GnomAD3 exomes

AF:

0.0419

AC:

10455

AN:

249694

Hom.:

624

AF XY:

0.0389

AC XY:

5250

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.0315

Gnomad ASJ exome

AF:

0.0338

Gnomad EAS exome

AF:

0.0171

Gnomad SAS exome

AF:

0.0292

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0291

Gnomad OTH exome

AF:

0.0334

GnomAD4 exome

AF:

0.0334

AC:

48714

AN:

1459680

Hom.:

1806

Cov.:

AF XY:

0.0330

AC XY:

23930

AN XY:

726182

show subpopulations

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.0340

Gnomad4 ASJ exome

AF:

0.0356

Gnomad4 EAS exome

AF:

0.0142

Gnomad4 SAS exome

AF:

0.0305

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.0280

Gnomad4 OTH exome

AF:

0.0443

GnomAD4 genome

AF:

0.0899

AC:

13675

AN:

152174

Hom.:

1336

Cov.:

AF XY:

0.0876

AC XY:

6521

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.0558

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.0183

Gnomad4 SAS

AF:

0.0311

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.0285

Gnomad4 OTH

AF:

0.0697

Alfa

AF:

0.0502

Hom.:

379

Bravo

AF:

0.100

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

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 22, 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

-0.57

CADD

Benign

8.3

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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