chr9-129856528-G-A

Variant names:

• chr9-129856528-G-A
• rs7862315
• NM_001110303.4:c.135+168G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001110303.4(USP20):​c.135+168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,312 control chromosomes in the GnomAD database, including 57,235 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (57235 hom., cov: 34)
• Consequence: USP20 NM_001110303.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP20	NM_001110303.4	MANE Select	c.135+168G>A		intron	N/A	NP_001103773.2
	USP20	NM_001008563.5		c.135+168G>A		intron	N/A	NP_001008563.2
	USP20	NM_006676.8		c.135+168G>A		intron	N/A	NP_006667.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP20	ENST00000372429.8	TSL:1 MANE Select	c.135+168G>A		intron	N/A	ENSP00000361506.3
	USP20	ENST00000315480.9	TSL:1	c.135+168G>A		intron	N/A	ENSP00000313811.4
	USP20	ENST00000358355.5	TSL:1	c.135+168G>A		intron	N/A	ENSP00000351122.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131539 AN: 152194 Hom.: 57198 Cov.: 34

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.862

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.864 AC: 131631 AN: 152312 Hom.: 57235 Cov.: 34 AF XY: 0.871 AC XY: 64887 AN XY: 74490

African (AFR) AF: 0.766 AC: 31802 AN: 41542

American (AMR) AF: 0.895 AC: 13698 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2966 AN: 3470

East Asian (EAS) AF: 0.977 AC: 5066 AN: 5186

South Asian (SAS) AF: 0.903 AC: 4365 AN: 4832

European-Finnish (FIN) AF: 0.947 AC: 10061 AN: 10626

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60941 AN: 68028

Other (OTH) AF: 0.862 AC: 1825 AN: 2116

Alfa AF: 0.894 Hom.: 82430

Bravo AF: 0.856

Asia WGS AF: 0.935 AC: 3251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.041
DANN	Benign	0.77
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7862315; hg19: chr9-132618807;