Genetic Variant USP43:p.Arg20Gly (chr17-9645690-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_153210.5(USP43):c.58C>G(p.Arg20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,292,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

USP43
NM_153210.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.551

Variant links:

Genes affected

USP43 (HGNC:20072): (ubiquitin specific peptidase 43) Predicted to enable ISG15-specific protease activity. Predicted to be involved in translesion synthesis. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

USP43 links:

CFAP52 (HGNC:16053): (cilia and flagella associated protein 52) WD repeat-containing proteins, such as WDR16, play crucial roles in a wide range of physiologic functions, including signal transduction, RNA processing, remodeling the cytoskeleton, regulation of vesicular traffic, and cell division (Silva et al., 2005 [PubMed 15967112]).[supplied by OMIM, Mar 2008]

CFAP52 links:

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=0.18467724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP43	NM_153210.5 link	c.58C>G	p.Arg20Gly	missense_variant	Exon 1 of 15	ENST00000285199.12	NP_694942.3	Q70EL4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP43	ENST00000285199.12 link	c.58C>G	p.Arg20Gly	missense_variant	Exon 1 of 15	1	NM_153210.5	ENSP00000285199.6	Q70EL4-1
USP43	ENST00000570475.5 link	c.58C>G	p.Arg20Gly	missense_variant	Exon 1 of 15	1		ENSP00000458963.1	Q70EL4-4
USP43	ENST00000570827.6 link	n.645+348C>G		intron_variant	Intron 1 of 14	2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151378

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000175

AC:

AN:

1141510

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

552248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

23002

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

9490

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

14898

Gnomad4 EAS exome

AF:

0.0000386

AC:

AN:

25886

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

35744

Gnomad4 FIN exome

AF:

0.0000405

AC:

AN:

24702

Gnomad4 NFE exome

AF:

0.0000188

AC:

AN:

959030

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

45708

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<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:

0.0000132

AC:

AN:

151378

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73926

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000295

AC:

0.0000295168

AN:

0.0000295168

Gnomad4 OTH

AF:

0.00

AC:

AN:

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 27, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.58C>G (p.R20G) alteration is located in exon 1 (coding exon 1) of the USP43 gene. This alteration results from a C to G substitution at nucleotide position 58, causing the arginine (R) at amino acid position 20 to be replaced by a glycine (G). 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

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.059

.;T

Eigen

Benign

-0.074

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.54

T;T

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.11

Sift

Uncertain

0.013

.;D

Sift4G

Uncertain

0.058

T;D

Polyphen

0.98

.;D

Vest4

0.16

MutPred

0.32

Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);

MVP

0.54

MPC

0.64

ClinPred

0.68

GERP RS

3.4

Varity_R

0.21

gMVP

0.57

Mutation Taster

=93/7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over