Variant chr12-62302818-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The ENST00000280377.10(USP15):c.246C>T(p.His82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,610,132 control chromosomes in the GnomAD database, including 77,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.33 ( 8904 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68210 hom. )

Consequence

USP15
ENST00000280377.10 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.28

Variant links:

Genes affected

USP15 (HGNC:12613): (ubiquitin specific peptidase 15) This gene encodes a member of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. USP enzymes play critical roles in ubiquitin-dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin-substrate bonds. The encoded protein associates with the COP9 signalosome, and also plays a role in transforming growth factor beta signalling through deubiquitination of receptor-activated SMAD transcription factors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 2. [provided by RefSeq, Nov 2011]

USP15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 12-62302818-C-T is Benign according to our data. Variant chr12-62302818-C-T is described in ClinVar as [Benign]. Clinvar id is 3060061.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP15	NM_001252078.2 linkuse as main transcript	c.246C>T	p.His82=	synonymous_variant	3/22	ENST00000280377.10	NP_001239007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP15	ENST00000280377.10 linkuse as main transcript	c.246C>T	p.His82=	synonymous_variant	3/22	1	NM_001252078.2	ENSP00000280377	P3	Q9Y4E8-1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50365

AN:

151808

Hom.:

8898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.280

AC:

70007

AN:

250460

Hom.:

10550

AF XY:

0.282

AC XY:

38120

AN XY:

135342

show subpopulations

Gnomad AFR exome

AF:

0.466

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.302

AC:

439880

AN:

1458206

Hom.:

68210

Cov.:

AF XY:

0.301

AC XY:

218693

AN XY:

725440

show subpopulations

Gnomad4 AFR exome

AF:

0.463

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.240

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.245

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.332

AC:

50386

AN:

151926

Hom.:

8904

Cov.:

AF XY:

0.326

AC XY:

24190

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.267

Gnomad4 ASJ

AF:

0.227

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.303

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.307

Hom.:

16400

Bravo

AF:

0.338

Asia WGS

AF:

0.224

AC:

782

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

USP15-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.2

DANN

Benign

0.56

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