NM_032172.3:c.529A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032172.3(USP42):​c.529A>G​(p.Met177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,605,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

USP42
NM_032172.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82

Publications

0 publications found
Variant links:
Genes affected
USP42 (HGNC:20068): (ubiquitin specific peptidase 42) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.075745344).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP42NM_032172.3 linkc.529A>G p.Met177Val missense_variant Exon 4 of 18 ENST00000306177.10 NP_115548.1 Q9H9J4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP42ENST00000306177.10 linkc.529A>G p.Met177Val missense_variant Exon 4 of 18 5 NM_032172.3 ENSP00000301962.5 Q9H9J4-2

Frequencies

GnomAD3 genomes
AF:
0.0000265
AC:
4
AN:
151050
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000244
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:
0.0000295
Gnomad OTH
AF:
0.000482
GnomAD2 exomes
AF:
0.00000407
AC:
1
AN:
245874
AF XY:
0.00000750
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1454812
Hom.:
0
Cov.:
29
AF XY:
0.00000276
AC XY:
2
AN XY:
723692
show subpopulations
African (AFR)
AF:
0.0000301
AC:
1
AN:
33240
American (AMR)
AF:
0.00
AC:
0
AN:
44160
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25992
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39540
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85128
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53220
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5740
European-Non Finnish (NFE)
AF:
0.00000181
AC:
2
AN:
1107760
Other (OTH)
AF:
0.00
AC:
0
AN:
60032
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000265
AC:
4
AN:
151050
Hom.:
0
Cov.:
30
AF XY:
0.0000136
AC XY:
1
AN XY:
73690
show subpopulations
African (AFR)
AF:
0.0000244
AC:
1
AN:
41058
American (AMR)
AF:
0.00
AC:
0
AN:
15124
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5164
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4798
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10232
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
0.0000295
AC:
2
AN:
67910
Other (OTH)
AF:
0.000482
AC:
1
AN:
2074
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000658
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 15, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.529A>G (p.M177V) alteration is located in exon 4 (coding exon 3) of the USP42 gene. This alteration results from a A to G substitution at nucleotide position 529, causing the methionine (M) at amino acid position 177 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
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Benign
0.92
DEOGEN2
Benign
0.010
.;T;T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.79
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.076
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.49
N;.;.
PhyloP100
2.8
PrimateAI
Benign
0.44
T
PROVEAN
Benign
0.49
N;N;N
REVEL
Benign
0.14
Sift
Benign
0.10
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.014
B;.;.
Vest4
0.17
MVP
0.23
MPC
1.8
ClinPred
0.19
T
GERP RS
4.0
gMVP
0.27
Mutation Taster
=96/4
polymorphism

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

Other links and lift over

dbSNP: rs1325512193; hg19: chr7-6175558; API