17-9645756-G-A

Variant summary

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

The NM_153210.5(USP43):​c.124G>A​(p.Gly42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000241 in 1,244,960 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: not found (cov: 32)
Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

USP43
NM_153210.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87
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]
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]

Genome browser will be placed here

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=0.0507392).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP43NM_153210.5 linkc.124G>A p.Gly42Arg missense_variant Exon 1 of 15 ENST00000285199.12 NP_694942.3 Q70EL4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USP43ENST00000285199.12 linkc.124G>A p.Gly42Arg missense_variant Exon 1 of 15 1 NM_153210.5 ENSP00000285199.6 Q70EL4-1
USP43ENST00000570475.5 linkc.124G>A p.Gly42Arg missense_variant Exon 1 of 15 1 ENSP00000458963.1 Q70EL4-4
USP43ENST00000570827.6 linkn.645+414G>A intron_variant Intron 1 of 14 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000288
AC:
1
AN:
34694
Hom.:
0
AF XY:
0.0000478
AC XY:
1
AN XY:
20934
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 SAS exome
AF:
0.000132
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000241
AC:
3
AN:
1244960
Hom.:
0
Cov.:
30
AF XY:
0.00000492
AC XY:
3
AN XY:
609872
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000365
Gnomad4 SAS exome
AF:
0.0000173
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000196
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.0000411
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.124G>A (p.G42R) alteration is located in exon 1 (coding exon 1) of the USP43 gene. This alteration results from a G to A substitution at nucleotide position 124, causing the glycine (G) at amino acid position 42 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
Benign
0.11
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.042
.;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.53
T;T
M_CAP
Uncertain
0.28
D
MetaRNN
Benign
0.051
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.63
N;N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-1.9
.;N
REVEL
Benign
0.070
Sift
Benign
0.060
.;T
Sift4G
Uncertain
0.0050
D;D
Polyphen
0.42
.;B
Vest4
0.061
MutPred
0.20
Gain of methylation at G42 (P = 0.0377);Gain of methylation at G42 (P = 0.0377);
MVP
0.36
MPC
0.59
ClinPred
0.060
T
GERP RS
0.26
Varity_R
0.13
gMVP
0.39

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: rs767001982; hg19: chr17-9549073; API