1-161161068-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001014443.3(USP21):​c.428C>T​(p.Ala143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

USP21
NM_001014443.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.723
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08621502).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP21NM_001014443.3 linkc.428C>T p.Ala143Val 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.428C>T p.Ala143Val missense_variant Exon 3 of 14 1 NM_001014443.3 ENSP00000356981.3 Q9UK80-1
USP21ENST00000289865.12 linkc.428C>T p.Ala143Val missense_variant Exon 2 of 13 1 ENSP00000289865.8 Q9UK80-1
USP21ENST00000368001.1 linkc.428C>T p.Ala143Val missense_variant Exon 2 of 13 1 ENSP00000356980.1 Q9UK80-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251316
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000611
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 01, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.428C>T (p.A143V) 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 428, causing the alanine (A) at amino acid position 143 to be replaced by a valine (V). 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
Benign
0.11
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0068
.;T;T;.
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.76
T;T;.;T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.086
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
.;N;N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.45
.;N;N;N
REVEL
Benign
0.051
Sift
Uncertain
0.0040
.;D;D;D
Sift4G
Benign
0.082
T;T;T;T
Polyphen
0.030
.;B;B;.
Vest4
0.14, 0.12, 0.11
MVP
0.43
MPC
0.11
ClinPred
0.20
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.069
gMVP
0.31

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: rs1266239809; hg19: chr1-161130858; API