USP20 p.Gly297Arg

Variant names:

• chr9-129868203-G-C
• NM_001110303.4:c.889G>C
• USP20 p.Gly297Arg

Your query was ambiguous. Multiple possible variants found:

• chr9-129868203-G-C
• chr9-129868203-G-A
• chr9-129868203-GGG-CGT
• chr9-129868203-GGG-CGC
• chr9-129868203-GGG-CGA
• chr9-129868203-GGG-AGA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001110303.4(USP20):​c.889G>C​(p.Gly297Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: USP20 NM_001110303.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23
• Publications: 0 publications found

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]

ACMG classification

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=0.20122132).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP20	NM_001110303.4	MANE Select	c.889G>C	p.Gly297Arg	missense	Exon 11 of 26	NP_001103773.2	Q9Y2K6
	USP20	NM_001008563.5		c.889G>C	p.Gly297Arg	missense	Exon 11 of 26	NP_001008563.2	Q9Y2K6
	USP20	NM_006676.8		c.889G>C	p.Gly297Arg	missense	Exon 11 of 25	NP_006667.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP20	ENST00000372429.8	TSL:1 MANE Select	c.889G>C	p.Gly297Arg	missense	Exon 11 of 26	ENSP00000361506.3	Q9Y2K6
	USP20	ENST00000315480.9	TSL:1	c.889G>C	p.Gly297Arg	missense	Exon 11 of 25	ENSP00000313811.4	Q9Y2K6
	USP20	ENST00000358355.5	TSL:1	c.889G>C	p.Gly297Arg	missense	Exon 11 of 26	ENSP00000351122.1	Q9Y2K6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 90

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.057
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.034	D
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Varity_R		0.12
gMVP		0.24
Mutation Taster		=73/27	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-132630482;