Genetic Variant USP43:p.Ala34Glu (chr17-9645733-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153210.5(USP43):c.101C>A(p.Ala34Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,371,698 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 0.00017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

USP43
NM_153210.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

situs inversus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
visceral heterotaxy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CFAP52 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20273444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153210.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP43	NM_153210.5	MANE Select	c.101C>A	p.Ala34Glu	missense	Exon 1 of 15	NP_694942.3
	USP43	NM_001267576.2		c.101C>A	p.Ala34Glu	missense	Exon 1 of 15	NP_001254505.1	Q70EL4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP43	ENST00000285199.12	TSL:1 MANE Select	c.101C>A	p.Ala34Glu	missense	Exon 1 of 15	ENSP00000285199.6	Q70EL4-1
USP43	ENST00000570475.5	TSL:1	c.101C>A	p.Ala34Glu	missense	Exon 1 of 15	ENSP00000458963.1	Q70EL4-4
USP43	ENST00000936734.1		c.101C>A	p.Ala34Glu	missense	Exon 1 of 15	ENSP00000606793.1

Frequencies

GnomAD3 genomes

AF:

0.000172

AC:

AN:

151464

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000658

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:

0.000962

GnomAD2 exomes

AF:

0.0000346

AC:

AN:

28862

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000738

AC:

AN:

1220234

Hom.:

Cov.:

AF XY:

0.00000503

AC XY:

AN XY:

596808

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

24102

American (AMR)

AF:

0.0000714

AC:

AN:

13998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18280

East Asian (EAS)

AF:

0.00

AC:

AN:

27138

South Asian (SAS)

AF:

0.00

AC:

AN:

53292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3450

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1000862

Other (OTH)

AF:

0.000101

AC:

AN:

49614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.000172

AC:

AN:

151464

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

73958

show subpopulations

African (AFR)

AF:

0.000339

AC:

AN:

41328

American (AMR)

AF:

0.000658

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67810

Other (OTH)

AF:

0.000962

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000147

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

Eigen

Benign

-0.019

Eigen_PC

Benign

-0.060

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

PhyloP100

2.5

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.20

REVEL

Benign

0.11

Sift

Uncertain

0.010

Sift4G

Uncertain

0.018

Polyphen

0.99

Vest4

0.21

MutPred

0.27

Gain of solvent accessibility (P = 0.0411)

MVP

0.47

MPC

0.58

ClinPred

0.28

GERP RS

2.1

PromoterAI

-0.010

Neutral

(source)

Varity_R

0.16

gMVP

0.33

Mutation Taster

=88/12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over