Variant chr12-62384284-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001252078.2(USP15):c.1455A>G(p.Pro485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,605,158 control chromosomes in the GnomAD database, including 300,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.59 ( 26317 hom., cov: 25)

Exomes 𝑓: 0.61 ( 274501 hom. )

Consequence

USP15
NM_001252078.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.273

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 12-62384284-A-G is Benign according to our data. Variant chr12-62384284-A-G is described in ClinVar as [Benign]. Clinvar id is 3060073.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.273 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 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.1455A>G	p.Pro485=	synonymous_variant	11/22	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.1455A>G	p.Pro485=	synonymous_variant	11/22	1	NM_001252078.2	ENSP00000280377	P3	Q9Y4E8-1
USP15	ENST00000353364.7 linkuse as main transcript	c.1368A>G	p.Pro456=	synonymous_variant	10/21	1		ENSP00000258123	A1	Q9Y4E8-2
USP15	ENST00000549268.1 linkuse as main transcript	n.813A>G		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

87854

AN:

147968

Hom.:

26311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.577

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.576

GnomAD3 exomes

AF:

0.604

AC:

149724

AN:

248070

Hom.:

45516

AF XY:

0.600

AC XY:

80553

AN XY:

134254

show subpopulations

Gnomad AFR exome

AF:

0.536

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.607

Gnomad SAS exome

AF:

0.524

Gnomad FIN exome

AF:

0.712

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.604

GnomAD4 exome

AF:

0.613

AC:

892510

AN:

1457116

Hom.:

274501

Cov.:

AF XY:

0.610

AC XY:

442302

AN XY:

724848

show subpopulations

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.594

Gnomad4 ASJ exome

AF:

0.566

Gnomad4 EAS exome

AF:

0.597

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.708

Gnomad4 NFE exome

AF:

0.621

Gnomad4 OTH exome

AF:

0.595

GnomAD4 genome

AF:

0.594

AC:

87874

AN:

148042

Hom.:

26317

Cov.:

AF XY:

0.595

AC XY:

42912

AN XY:

72066

show subpopulations

Gnomad4 AFR

AF:

0.534

Gnomad4 AMR

AF:

0.577

Gnomad4 ASJ

AF:

0.567

Gnomad4 EAS

AF:

0.587

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.718

Gnomad4 NFE

AF:

0.624

Gnomad4 OTH

AF:

0.570

Alfa

AF:

0.609

Hom.:

17052

Bravo

AF:

0.584

Asia WGS

AF:

0.525

AC:

1831

AN:

3478

EpiCase

AF:

0.606

EpiControl

AF:

0.606

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

-0.63

CADD

Benign

4.5

DANN

Benign

0.34

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