NM_003363.4:c.2627C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003363.4(USP4):​c.2627C>T​(p.Ala876Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A876D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

USP4
NM_003363.4 missense

Scores

2
9
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.14
Variant links:
Genes affected
USP4 (HGNC:12627): (ubiquitin specific peptidase 4) The protein encoded by this gene is a protease that deubiquitinates target proteins such as ADORA2A and TRIM21. The encoded protein shuttles between the nucleus and cytoplasm and is involved in maintaining operational fidelity in the endoplasmic reticulum. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP4NM_003363.4 linkc.2627C>T p.Ala876Val missense_variant Exon 20 of 22 ENST00000265560.9 NP_003354.2 Q13107-1A1LPW7Q08AK7
USP4NM_199443.3 linkc.2486C>T p.Ala829Val missense_variant Exon 19 of 21 NP_955475.1 Q13107-2A0A024R2X6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP4ENST00000265560.9 linkc.2627C>T p.Ala876Val missense_variant Exon 20 of 22 1 NM_003363.4 ENSP00000265560.4 Q13107-1
USP4ENST00000351842.8 linkc.2486C>T p.Ala829Val missense_variant Exon 19 of 21 1 ENSP00000341028.4 Q13107-2
USP4ENST00000431357.1 linkc.1841C>T p.Ala614Val missense_variant Exon 14 of 15 5 ENSP00000399079.1 H7C189
USP4ENST00000485450.5 linkn.3141C>T non_coding_transcript_exon_variant Exon 14 of 16 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251410
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461748
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000364
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.61
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.25
.;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.014
T
MetaRNN
Uncertain
0.45
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
.;L
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Benign
0.16
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.79
P;P
Vest4
0.53
MutPred
0.64
.;Gain of glycosylation at Y874 (P = 0.11);
MVP
0.70
MPC
0.20
ClinPred
0.93
D
GERP RS
5.6
Varity_R
0.69
gMVP
0.42

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: rs775772757; hg19: chr3-49318194; API