Genetic Variant USP20:p.Asp6Gly (chr9-129852572-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001110303.4(USP20):c.17A>G(p.Asp6Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D6V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

USP20
NM_001110303.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.40

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121007234).

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.17A>G	p.Asp6Gly	missense	Exon 3 of 26	NP_001103773.2	Q9Y2K6
USP20	NM_001008563.5		c.17A>G	p.Asp6Gly	missense	Exon 3 of 26	NP_001008563.2	Q9Y2K6
USP20	NM_006676.8		c.17A>G	p.Asp6Gly	missense	Exon 3 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.17A>G	p.Asp6Gly	missense	Exon 3 of 26	ENSP00000361506.3	Q9Y2K6
USP20	ENST00000315480.9	TSL:1	c.17A>G	p.Asp6Gly	missense	Exon 3 of 25	ENSP00000313811.4	Q9Y2K6
USP20	ENST00000358355.5	TSL:1	c.17A>G	p.Asp6Gly	missense	Exon 3 of 26	ENSP00000351122.1	Q9Y2K6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1445950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717590

African (AFR)

AF:

0.00

AC:

AN:

33228

American (AMR)

AF:

0.00

AC:

AN:

42758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25748

East Asian (EAS)

AF:

0.00

AC:

AN:

39310

South Asian (SAS)

AF:

0.00

AC:

AN:

83400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103702

Other (OTH)

AF:

0.00

AC:

AN:

59786

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

Eigen

Benign

0.12

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.58

M_CAP

Benign

0.0088

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

5.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.5

REVEL

Benign

0.047

Sift

Benign

0.033

Sift4G

Benign

0.076

Polyphen

0.75

Vest4

0.098

MutPred

0.14

Loss of stability (P = 0.0684)

MVP

0.45

MPC

0.40

ClinPred

0.83

GERP RS

4.5

Varity_R

0.16

gMVP

0.62

Mutation Taster

=52/48

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over