Genetic Variant USP43:p.Pro13Arg (chr17-9645670-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153210.5(USP43):c.38C>G(p.Pro13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,272,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. P13L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

USP43
NM_153210.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

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:

LOC124903924 (HGNC:):

LOC124903924 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05872065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP43	NM_153210.5 link	c.38C>G	p.Pro13Arg	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.38C>G	p.Pro13Arg	missense_variant	Exon 1 of 15	1	NM_153210.5	ENSP00000285199.6	Q70EL4-1
USP43	ENST00000570475.5 link	c.38C>G	p.Pro13Arg	missense_variant	Exon 1 of 15	1		ENSP00000458963.1	Q70EL4-4
USP43	ENST00000570827.6 link	n.645+328C>G		intron_variant	Intron 1 of 14	2

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.92e-7

AC:

AN:

1121474

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

540724

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000106

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151292

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73886

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.33

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.53

.;N

REVEL

Benign

0.0090

Sift

Benign

0.74

.;T

Sift4G

Uncertain

0.018

D;D

Polyphen

0.015

.;B

Vest4

0.064

MutPred

0.28

Gain of methylation at P13 (P = 0.0022);Gain of methylation at P13 (P = 0.0022);

MVP

0.47

MPC

0.53

ClinPred

0.018

GERP RS

-0.16

Varity_R

0.036

gMVP

0.29

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over