dbSNP rs376684663: USP20:p.Gly302Arg (chr9-129868218-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001110303.4(USP20):c.904G>A(p.Gly302Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

USP20
NM_001110303.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

Publications

0 publications found

Variant links:

Genes affected

USP20 (HGNC:12619): (ubiquitin specific peptidase 20) This gene encodes a ubiquitin specific processing protease that was first identified as a substrate of the VHL (von Hippel-Lindau disease) protein E3 ubiquitin ligase complex. In addition to being ubiquitinated by the VHL-E3 ligase complex, this enzyme deubiquitinates hypoxia-inducible factor (HIF)-1 alpha and thereby causes increased expression of HIF-1alpha targeted genes which play a role in angiogenesis, glucose metabolism, cell proliferation and metastasis. The enzyme encoded by this gene also regulates G-protein coupled receptor signaling by mediating the deubiquitination of beta-2 adrenergic receptor (ADRB2). This enzyme is a ubiquitously expressed thiolester hydrolase. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jan 2013]

USP20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027565897).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110303.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP20	NM_001110303.4	MANE Select	c.904G>A	p.Gly302Arg	missense	Exon 11 of 26	NP_001103773.2	Q9Y2K6
USP20	NM_001008563.5		c.904G>A	p.Gly302Arg	missense	Exon 11 of 26	NP_001008563.2	Q9Y2K6
USP20	NM_006676.8		c.904G>A	p.Gly302Arg	missense	Exon 11 of 25	NP_006667.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP20	ENST00000372429.8	TSL:1 MANE Select	c.904G>A	p.Gly302Arg	missense	Exon 11 of 26	ENSP00000361506.3	Q9Y2K6
USP20	ENST00000315480.9	TSL:1	c.904G>A	p.Gly302Arg	missense	Exon 11 of 25	ENSP00000313811.4	Q9Y2K6
USP20	ENST00000358355.5	TSL:1	c.904G>A	p.Gly302Arg	missense	Exon 11 of 26	ENSP00000351122.1	Q9Y2K6

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000153

AC:

AN:

248776

AF XY:

0.000230

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000975

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

147

AN:

1461594

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.000112

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000985

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

1111872

Other (OTH)

AF:

0.0000828

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000873

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000149

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.017

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.73

M_CAP

Benign

0.0045

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.36

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.77

REVEL

Benign

0.087

Sift

Benign

0.43

Sift4G

Benign

0.61

Polyphen

0.0010

Vest4

0.23

MutPred

0.51

Gain of methylation at G302 (P = 0.0402)

MVP

0.38

MPC

0.37

ClinPred

0.026

GERP RS

1.8

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

4.0

Varity_R

0.034

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over