Genetic Variant USP21:p.Arg145Gly (chr1-161161073-C-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_001014443.3(USP21):c.433C>G(p.Arg145Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. R145W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

USP21
NM_001014443.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Publications

0 publications found

Variant links:

Genes affected

USP21 (HGNC:12620): (ubiquitin specific peptidase 21) This gene encodes a member of the C19 peptidase family, also known as family 2 of ubiquitin carboxy-terminal hydrolases. The encoded protein cleaves ubiquitin from ubiquitinated proteins for recycling in intracellular protein degradation. The encoded protein is also able to release NEDD8, a ubiquitin-like protein, from NEDD8-conjugated proteins. This gene has been referred to as USP16 and USP23 but is now known as USP21. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

USP21 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=0.18193293).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014443.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP21	NM_001014443.3	MANE Select	c.433C>G	p.Arg145Gly	missense	Exon 3 of 14	NP_001014443.1	Q9UK80-1
USP21	NM_001319847.2		c.520C>G	p.Arg174Gly	missense	Exon 2 of 13	NP_001306776.1
USP21	NM_012475.5		c.433C>G	p.Arg145Gly	missense	Exon 2 of 13	NP_036607.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP21	ENST00000368002.8	TSL:1 MANE Select	c.433C>G	p.Arg145Gly	missense	Exon 3 of 14	ENSP00000356981.3	Q9UK80-1
USP21	ENST00000289865.12	TSL:1	c.433C>G	p.Arg145Gly	missense	Exon 2 of 13	ENSP00000289865.8	Q9UK80-1
USP21	ENST00000368001.1	TSL:1	c.433C>G	p.Arg145Gly	missense	Exon 2 of 13	ENSP00000356980.1	Q9UK80-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

251328

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000197

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

1.5

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.030

REVEL

Benign

0.25

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

0.88

Vest4

0.73

MutPred

0.27

Loss of MoRF binding (P = 0.0141)

MVP

0.57

MPC

0.22

ClinPred

0.50

GERP RS

4.0

Varity_R

0.11

gMVP

0.60

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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