9-129858576-C-A

Position:

chr9-129858576-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001110303.4(USP20):c.308C>A(p.Ser103Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00129 in 1,614,062 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00082 ( 14 hom. )

Consequence

USP20
NM_001110303.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.07

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035541654).

BP6

Variant 9-129858576-C-A is Benign according to our data. Variant chr9-129858576-C-A is described in ClinVar as [Benign]. Clinvar id is 717919.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00588 (895/152340) while in subpopulation AFR AF= 0.0197 (818/41572). AF 95% confidence interval is 0.0186. There are 8 homozygotes in gnomad4. There are 442 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USP20	NM_001110303.4 linkuse as main transcript	c.308C>A	p.Ser103Tyr	missense_variant	6/26	ENST00000372429.8
USP20	NM_001008563.5 linkuse as main transcript	c.308C>A	p.Ser103Tyr	missense_variant	6/26
USP20	NM_006676.8 linkuse as main transcript	c.308C>A	p.Ser103Tyr	missense_variant	6/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
USP20	ENST00000372429.8 linkuse as main transcript	c.308C>A	p.Ser103Tyr	missense_variant	6/26	1	NM_001110303.4	P1
USP20	ENST00000315480.9 linkuse as main transcript	c.308C>A	p.Ser103Tyr	missense_variant	6/25	1		P1
USP20	ENST00000358355.5 linkuse as main transcript	c.308C>A	p.Ser103Tyr	missense_variant	6/26	1		P1
USP20	ENST00000494971.2 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

892

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000411

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00173

AC:

431

AN:

249278

Hom.:

AF XY:

0.00140

AC XY:

190

AN XY:

135252

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000610

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000815

AC:

1192

AN:

1461722

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

553

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000267

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00588

AC:

895

AN:

152340

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

442

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0197

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00663

ESP6500AA

AF:

0.0176

AC:

ESP6500EA

AF:

0.000357

AC:

ExAC

AF:

0.00212

AC:

256

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00130

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.022

T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.93

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.73

N;N;N

REVEL

Benign

0.093

Sift

Benign

0.22

T;T;T

Sift4G

Uncertain

0.038

D;D;D

Polyphen

0.16

B;B;B

Vest4

0.33

MVP

0.44

MPC

0.44

ClinPred

0.039

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.067

gMVP

0.39

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