chr17-9645670-C-T

Variant names:

Variant summary

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

The NM_153210.5(USP43):c.38C>T(p.Pro13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000535 in 1,121,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P13Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000054 ( 0 hom. )

Consequence

USP43
NM_153210.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0100

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:

LOC124903924 (HGNC:):

LOC124903924 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=0.06802854).

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.38C>T	p.Pro13Leu	missense	Exon 1 of 15	NP_694942.3
	USP43	NM_001267576.2		c.38C>T	p.Pro13Leu	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.38C>T	p.Pro13Leu	missense	Exon 1 of 15	ENSP00000285199.6	Q70EL4-1
USP43	ENST00000570475.5	TSL:1	c.38C>T	p.Pro13Leu	missense	Exon 1 of 15	ENSP00000458963.1	Q70EL4-4
USP43	ENST00000936734.1		c.38C>T	p.Pro13Leu	missense	Exon 1 of 15	ENSP00000606793.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000535

AC:

AN:

1121474

Hom.:

Cov.:

AF XY:

0.00000925

AC XY:

AN XY:

540724

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22540

American (AMR)

AF:

0.00

AC:

AN:

8368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14096

East Asian (EAS)

AF:

0.00

AC:

AN:

25160

South Asian (SAS)

AF:

0.00

AC:

AN:

32378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2952

European-Non Finnish (NFE)

AF:

0.00000528

AC:

AN:

947796

Other (OTH)

AF:

0.0000225

AC:

AN:

44476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.030

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.42

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

PhyloP100

-0.010

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.4

REVEL

Benign

0.0070

Sift

Benign

0.48

Sift4G

Benign

0.11

Polyphen

0.033

Vest4

0.066

MutPred

0.21

Loss of relative solvent accessibility (P = 0.0306)

MVP

0.51

MPC

0.51

ClinPred

0.068

GERP RS

-0.16

PromoterAI

-0.0081

Neutral

(source)

Varity_R

0.034

gMVP

0.33

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over