Variant 9-129868415-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001110303.4(USP20):c.1101G>A(p.Pro367=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,612,016 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 154 hom. )

Consequence

USP20
NM_001110303.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-129868415-G-A is Benign according to our data. Variant chr9-129868415-G-A is described in ClinVar as [Benign]. Clinvar id is 790844.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.67 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00305 (464/152122) while in subpopulation SAS AF= 0.0535 (258/4822). AF 95% confidence interval is 0.0481. There are 8 homozygotes in gnomad4. There are 310 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.1101G>A	p.Pro367=	synonymous_variant	11/26	ENST00000372429.8
USP20	NM_001008563.5 linkuse as main transcript	c.1101G>A	p.Pro367=	synonymous_variant	11/26
USP20	NM_006676.8 linkuse as main transcript	c.1101G>A	p.Pro367=	synonymous_variant	11/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP20	ENST00000372429.8 linkuse as main transcript	c.1101G>A	p.Pro367=	synonymous_variant	11/26	1	NM_001110303.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000701

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00387

Gnomad SAS

AF:

0.0533

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00751

AC:

1824

AN:

242966

Hom.:

AF XY:

0.00963

AC XY:

1282

AN XY:

133082

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.00248

Gnomad ASJ exome

AF:

0.00771

Gnomad EAS exome

AF:

0.00298

Gnomad SAS exome

AF:

0.0484

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000910

Gnomad OTH exome

AF:

0.00522

GnomAD4 exome

AF:

0.00400

AC:

5843

AN:

1459894

Hom.:

154

Cov.:

AF XY:

0.00538

AC XY:

3908

AN XY:

726206

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.00678

Gnomad4 EAS exome

AF:

0.00144

Gnomad4 SAS exome

AF:

0.0476

Gnomad4 FIN exome

AF:

0.0000766

Gnomad4 NFE exome

AF:

0.000992

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.00305

AC:

464

AN:

152122

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

310

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000699

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00408

Gnomad4 SAS

AF:

0.0535

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00162

Asia WGS

AF:

0.0290

AC:

103

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000948

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

May 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.34

DANN

Benign

0.59

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