17-9645868-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.236G>A​(p.Arg79His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000843 in 1,423,740 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

USP43
NM_153210.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.123
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]

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=0.06302306).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USP43NM_153210.5 linkc.236G>A p.Arg79His 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.236G>A p.Arg79His missense_variant Exon 1 of 15 1 NM_153210.5 ENSP00000285199.6 Q70EL4-1
USP43ENST00000570475.5 linkc.236G>A p.Arg79His missense_variant Exon 1 of 15 1 ENSP00000458963.1 Q70EL4-4
USP43ENST00000570827.6 linkn.645+526G>A intron_variant Intron 1 of 14 2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
151974
Hom.:
0
Cov.:
32
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:
0.000969
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:
0.00000550
AC:
7
AN:
1271658
Hom.:
0
Cov.:
30
AF XY:
0.00000805
AC XY:
5
AN XY:
621326
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000216
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000192
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152082
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000972
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.236G>A (p.R79H) 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 236, causing the arginine (R) at amino acid position 79 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
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.037
.;T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.063
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.97
L;L
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-1.0
.;N
REVEL
Benign
0.039
Sift
Uncertain
0.0040
.;D
Sift4G
Benign
0.088
T;T
Polyphen
0.0060
.;B
Vest4
0.15
MutPred
0.25
Loss of methylation at R79 (P = 0.0283);Loss of methylation at R79 (P = 0.0283);
MVP
0.38
MPC
1.1
ClinPred
0.50
T
GERP RS
0.80
Varity_R
0.084
gMVP
0.16

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: rs530371655; hg19: chr17-9549185; API