Variant rs3088040 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001385174.1(USP36):c.2417A>G(p.Gln806Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,612,380 control chromosomes in the GnomAD database, including 249,854 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.57 ( 24597 hom., cov: 32)

Exomes 𝑓: 0.55 ( 225257 hom. )

Consequence

USP36
NM_001385174.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

Variant links:

Genes affected

USP36 (HGNC:20062): (ubiquitin specific peptidase 36) This gene encodes a member of the peptidase C19 or ubiquitin-specific protease family of cysteine proteases. Members of this family remove ubiquitin molecules from polyubiquitinated proteins. The encoded protein may deubiquitinate and stabilize the transcription factor c-Myc, also known as MYC, an important oncoprotein known to be upregulated in most human cancers. The encoded protease may also regulate the activation of autophagy. This gene exhibits elevated expression in some breast and lung cancers. [provided by RefSeq, Mar 2016]

USP36 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 (MetaRNN=4.7939056E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP36	NM_001385174.1 linkuse as main transcript	c.2417A>G	p.Gln806Arg	missense_variant	16/21	ENST00000449938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP36	ENST00000449938.7 linkuse as main transcript	c.2417A>G	p.Gln806Arg	missense_variant	16/21	1	NM_001385174.1	P1

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86337

AN:

151920

Hom.:

24567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.626

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.552

GnomAD3 exomes

AF:

0.549

AC:

135362

AN:

246648

Hom.:

37511

AF XY:

0.546

AC XY:

73474

AN XY:

134590

show subpopulations

Gnomad AFR exome

AF:

0.601

Gnomad AMR exome

AF:

0.469

Gnomad ASJ exome

AF:

0.553

Gnomad EAS exome

AF:

0.604

Gnomad SAS exome

AF:

0.506

Gnomad FIN exome

AF:

0.636

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.535

GnomAD4 exome

AF:

0.554

AC:

808789

AN:

1460342

Hom.:

225257

Cov.:

AF XY:

0.552

AC XY:

401053

AN XY:

726472

show subpopulations

Gnomad4 AFR exome

AF:

0.598

Gnomad4 AMR exome

AF:

0.469

Gnomad4 ASJ exome

AF:

0.556

Gnomad4 EAS exome

AF:

0.612

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.626

Gnomad4 NFE exome

AF:

0.555

Gnomad4 OTH exome

AF:

0.549

GnomAD4 genome

AF:

0.568

AC:

86433

AN:

152038

Hom.:

24597

Cov.:

AF XY:

0.571

AC XY:

42422

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.594

Gnomad4 AMR

AF:

0.503

Gnomad4 ASJ

AF:

0.543

Gnomad4 EAS

AF:

0.611

Gnomad4 SAS

AF:

0.534

Gnomad4 FIN

AF:

0.626

Gnomad4 NFE

AF:

0.562

Gnomad4 OTH

AF:

0.554

Alfa

AF:

0.548

Hom.:

43308

Bravo

AF:

0.552

TwinsUK

AF:

0.556

AC:

2061

ALSPAC

AF:

0.561

AC:

2161

ESP6500AA

AF:

0.572

AC:

2477

ESP6500EA

AF:

0.545

AC:

4634

ExAC

AF:

0.545

AC:

65732

Asia WGS

AF:

0.606

AC:

2107

AN:

3476

EpiCase

AF:

0.546

EpiControl

AF:

0.550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

Cadd

Benign

0.019

Dann

Benign

0.13

DEOGEN2

Benign

0.0086

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.022

MetaRNN

Benign

0.0000048

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.95

L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.0030

Sift

Benign

0.95

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.0

B;B

Vest4

0.018

MPC

0.075

ClinPred

0.0096

GERP RS

-8.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over