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9-129868178-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001110303.4(USP20):c.864G>A(p.Ser288=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,614,064 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0032 ( 9 hom. )

Consequence

USP20
NM_001110303.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.25
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-129868178-G-A is Benign according to our data. Variant chr9-129868178-G-A is described in ClinVar as [Benign]. Clinvar id is 707949.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.25 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
USP20NM_001110303.4 linkuse as main transcriptc.864G>A p.Ser288= synonymous_variant 11/26 ENST00000372429.8
USP20NM_001008563.5 linkuse as main transcriptc.864G>A p.Ser288= synonymous_variant 11/26
USP20NM_006676.8 linkuse as main transcriptc.864G>A p.Ser288= synonymous_variant 11/25

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
USP20ENST00000372429.8 linkuse as main transcriptc.864G>A p.Ser288= synonymous_variant 11/261 NM_001110303.4 P1
USP20ENST00000315480.9 linkuse as main transcriptc.864G>A p.Ser288= synonymous_variant 11/251 P1
USP20ENST00000358355.5 linkuse as main transcriptc.864G>A p.Ser288= synonymous_variant 11/261 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00223
AC:
339
AN:
152168
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00130
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.00157
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00340
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00185
AC:
461
AN:
249346
Hom.:
0
AF XY:
0.00177
AC XY:
240
AN XY:
135292
show subpopulations
Gnomad AFR exome
AF:
0.00129
Gnomad AMR exome
AF:
0.00116
Gnomad ASJ exome
AF:
0.00308
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.000743
Gnomad NFE exome
AF:
0.00299
Gnomad OTH exome
AF:
0.00215
GnomAD4 exome
AF:
0.00325
AC:
4750
AN:
1461778
Hom.:
9
Cov.:
90
AF XY:
0.00304
AC XY:
2214
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.00152
Gnomad4 AMR exome
AF:
0.00125
Gnomad4 ASJ exome
AF:
0.00329
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000232
Gnomad4 FIN exome
AF:
0.00103
Gnomad4 NFE exome
AF:
0.00379
Gnomad4 OTH exome
AF:
0.00442
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00223
AC:
339
AN:
152286
Hom.:
1
Cov.:
33
AF XY:
0.00189
AC XY:
141
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.00130
Gnomad4 AMR
AF:
0.00157
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.00340
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00299
Hom.:
3
Bravo
AF:
0.00243
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

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 submitterclinical testingInvitaeMay 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
Cadd
Benign
0.27
Dann
Benign
0.79

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.

Other links and lift over

dbSNP: rs61760212; hg19: chr9-132630457; API