1-161160671-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001014443.3(USP21):​c.31C>T​(p.Arg11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

USP21
NM_001014443.3 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18867853).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP21NM_001014443.3 linkc.31C>T p.Arg11Cys missense_variant Exon 3 of 14 ENST00000368002.8 NP_001014443.1 Q9UK80-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP21ENST00000368002.8 linkc.31C>T p.Arg11Cys missense_variant Exon 3 of 14 1 NM_001014443.3 ENSP00000356981.3 Q9UK80-1
USP21ENST00000289865.12 linkc.31C>T p.Arg11Cys missense_variant Exon 2 of 13 1 ENSP00000289865.8 Q9UK80-1
USP21ENST00000368001.1 linkc.31C>T p.Arg11Cys missense_variant Exon 2 of 13 1 ENSP00000356980.1 Q9UK80-3

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
251094
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000862
AC:
126
AN:
1461736
Hom.:
0
Cov.:
31
AF XY:
0.0000770
AC XY:
56
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000104
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000680
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.31C>T (p.R11C) alteration is located in exon 3 (coding exon 1) of the USP21 gene. This alteration results from a C to T substitution at nucleotide position 31, causing the arginine (R) at amino acid position 11 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.021
.;T;T;T;.
Eigen
Benign
0.19
Eigen_PC
Benign
0.21
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.92
D;D;.;D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.19
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
.;N;N;.;N
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.93
.;N;N;.;N
REVEL
Benign
0.19
Sift
Pathogenic
0.0
.;D;D;.;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
.;D;D;.;.
Vest4
0.74, 0.73, 0.74
MVP
0.54
MPC
0.62
ClinPred
0.16
T
GERP RS
3.3
Varity_R
0.21
gMVP
0.50

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: rs149985789; hg19: chr1-161130461; COSMIC: COSV57091140; COSMIC: COSV57091140; API