Genetic Variant USP42:p.Arg191His (chr7-6139110-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032172.3(USP42):c.572G>A(p.Arg191His) variant causes a missense change. The variant allele was found at a frequency of 0.0000193 in 1,608,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R191C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

USP42
NM_032172.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42

Publications

1 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]

USP42 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
USP42	NM_032172.3 link	c.572G>A	p.Arg191His	missense_variant	Exon 5 of 18	ENST00000306177.10	NP_115548.1	Q9H9J4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP42	ENST00000306177.10 link	c.572G>A	p.Arg191His	missense_variant	Exon 5 of 18	5	NM_032172.3	ENSP00000301962.5		Q9H9J4-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152152

Hom.:

Cov.:

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000166

AC:

AN:

241284

AF XY:

0.00000765

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:

0.0000365

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1456430

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

723972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33388

American (AMR)

AF:

0.00

AC:

AN:

43992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

84882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53142

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1109566

Other (OTH)

AF:

0.0000498

AC:

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 18, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.572G>A (p.R191H) alteration is located in exon 5 (coding exon 4) of the USP42 gene. This alteration results from a G to A substitution at nucleotide position 572, causing the arginine (R) at amino acid position 191 to be replaced by a histidine (H). 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

Uncertain

0.087

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

.;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

L;.;.

PhyloP100

5.4

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Benign

0.29

Sift

Benign

0.24

T;T;T

Sift4G

Uncertain

0.053

T;T;T

Polyphen

0.84

P;.;.

Vest4

0.13

MutPred

0.56

Loss of MoRF binding (P = 0.0116);.;.;

MVP

0.42

MPC

1.6

ClinPred

0.97

GERP RS

5.4

gMVP

0.56

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr7-6139110-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over