4-143185931-G-A

Variant summary

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

The NM_032557.6(USP38):​c.481G>A​(p.Gly161Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

USP38
NM_032557.6 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90
Variant links:
Genes affected
USP38 (HGNC:20067): (ubiquitin specific peptidase 38) Enables thiol-dependent deubiquitinase. Involved in protein deubiquitination. 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 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
USP38NM_032557.6 linkc.481G>A p.Gly161Arg missense_variant Exon 1 of 10 ENST00000307017.9 NP_115946.2 Q8NB14-1
USP38NM_001410848.1 linkc.481G>A p.Gly161Arg missense_variant Exon 1 of 9 NP_001397777.1
USP38NM_001290325.1 linkc.481G>A p.Gly161Arg missense_variant Exon 1 of 9 NP_001277254.1 Q8NB14-2
USP38NM_001290326.1 linkc.-1001G>A 5_prime_UTR_variant Exon 1 of 11 NP_001277255.1 Q8NB14B3KSB9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP38ENST00000307017.9 linkc.481G>A p.Gly161Arg missense_variant Exon 1 of 10 1 NM_032557.6 ENSP00000303434.4 Q8NB14-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
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:
0.0000239
AC:
6
AN:
251442
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
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:
0.00000547
AC:
8
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.000169
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:
0.000164
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 18, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.481G>A (p.G161R) alteration is located in exon 1 (coding exon 1) of the USP38 gene. This alteration results from a G to A substitution at nucleotide position 481, causing the glycine (G) at amino acid position 161 to be replaced by an arginine (R). 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
Pathogenic
0.74
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
.;T
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.055
D
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.0
M;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.011
D;D
Polyphen
1.0
.;D
Vest4
0.50
MutPred
0.65
Gain of methylation at K162 (P = 0.0409);Gain of methylation at K162 (P = 0.0409);
MVP
0.85
MPC
0.59
ClinPred
0.64
D
GERP RS
4.9
Varity_R
0.53
gMVP
0.41

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: rs370661676; hg19: chr4-144107084; API