rs371329389

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001131016.2(CIZ1):c.353C>T(p.Thr118Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000685 in 730,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38

Publications

1 publications found

Variant links:

Genes affected

CIZ1 (HGNC:16744): (CDKN1A interacting zinc finger protein 1) The protein encoded by this gene is a zinc finger DNA binding protein that interacts with CIP1, part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CIZ1 Gene-Disease associations (from GenCC):

dystonia 23
Inheritance: Unknown Classification: MODERATE Submitted by: Genomics England PanelApp
inherited dystonia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CIZ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13152698).

BS2

High AC in GnomAd4 at 10 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIZ1	NM_001131016.2 link	c.353C>T	p.Thr118Ile	missense_variant	Exon 4 of 17	ENST00000372938.10	NP_001124488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000372938.10 link	c.353C>T	p.Thr118Ile	missense_variant	Exon 4 of 17	1	NM_001131016.2	ENSP00000362029.5

Frequencies

GnomAD3 genomes

AF:

0.0000668

AC:

AN:

149734

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000376

AC:

AN:

239656

AF XY:

0.0000230

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000838

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000689

AC:

AN:

580548

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

317362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17002

American (AMR)

AF:

0.00

AC:

AN:

41766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19804

East Asian (EAS)

AF:

0.00

AC:

AN:

35190

South Asian (SAS)

AF:

0.00

AC:

AN:

60212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2658

European-Non Finnish (NFE)

AF:

0.000114

AC:

AN:

323156

Other (OTH)

AF:

0.0000985

AC:

AN:

30464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000668

AC:

AN:

149734

Hom.:

Cov.:

AF XY:

0.0000822

AC XY:

AN XY:

72998

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41002

American (AMR)

AF:

0.00

AC:

AN:

14994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.000148

AC:

AN:

67568

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000225

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dystonic disorder

Uncertain:1

Aug 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 118 of the CIZ1 protein (p.Thr118Ile). This variant is present in population databases (rs371329389, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CIZ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 406207). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

.;T;T;.;T;.;T;T;T;.

Eigen

Benign

-0.050

Eigen_PC

Benign

0.0085

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.78

T;T;T;T;.;T;.;T;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.8

.;.;.;.;.;L;L;L;.;.

PhyloP100

3.4

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.92

.;N;.;.;N;N;N;.;N;N

REVEL

Benign

0.12

Sift

Benign

0.20

.;T;.;.;T;T;T;.;T;D

Sift4G

Uncertain

0.018

D;T;T;D;T;T;T;T;.;.

Polyphen

0.48, 0.62, 0.45

.;P;.;.;P;P;P;P;.;.

Vest4

0.57

MVP

0.75

MPC

0.52

ClinPred

0.16

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.21

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over