rs12334

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001131016.2(CIZ1):c.1733C>T(p.Ser578Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,591,550 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S578S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.025 ( 154 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 132 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.42

Publications

5 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018073916).

BP6

Variant 9-128177651-G-A is Benign according to our data. Variant chr9-128177651-G-A is described in ClinVar as Benign. ClinVar VariationId is 413839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIZ1	NM_001131016.2 link	c.1733C>T	p.Ser578Phe	missense_variant	Exon 10 of 17	ENST00000372938.10	NP_001124488.1	Q9ULV3-1A0A024R885

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000372938.10 link	c.1733C>T	p.Ser578Phe	missense_variant	Exon 10 of 17	1	NM_001131016.2	ENSP00000362029.5		Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3772

AN:

152138

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0862

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.00668

AC:

1414

AN:

211726

AF XY:

0.00487

show subpopulations

Gnomad AFR exome

AF:

0.0885

Gnomad AMR exome

AF:

0.00519

Gnomad ASJ exome

AF:

0.00759

Gnomad EAS exome

AF:

0.0000631

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.00487

GnomAD4 exome

AF:

0.00263

AC:

3783

AN:

1439294

Hom.:

132

Cov.:

AF XY:

0.00231

AC XY:

1648

AN XY:

713814

show subpopulations

African (AFR)

AF:

0.0877

AC:

2900

AN:

33062

American (AMR)

AF:

0.00540

AC:

222

AN:

41118

Ashkenazi Jewish (ASJ)

AF:

0.00726

AC:

186

AN:

25622

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38558

South Asian (SAS)

AF:

0.000157

AC:

AN:

82764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51616

Middle Eastern (MID)

AF:

0.00262

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000108

AC:

119

AN:

1101368

Other (OTH)

AF:

0.00550

AC:

327

AN:

59466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

179

357

536

714

893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.0248

AC:

3782

AN:

152256

Hom.:

154

Cov.:

AF XY:

0.0239

AC XY:

1776

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0862

AC:

3581

AN:

41536

American (AMR)

AF:

0.00713

AC:

109

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68018

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

176

353

529

706

882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0103

Hom.:

113

Bravo

AF:

0.0283

ESP6500AA

AF:

0.0888

AC:

390

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00757

AC:

916

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dystonic disorder

Benign:1

Jan 17, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

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

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.91

D;D;D;D;D;.;D;.;D;D

MetaRNN

Benign

0.0018

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

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

PhyloP100

2.4

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

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

REVEL

Benign

0.037

Sift

Uncertain

0.0020

D;.;D;.;.;D;D;D;.;D

Sift4G

Benign

0.081

T;D;D;D;D;D;D;D;D;D

Polyphen

0.93

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

Vest4

0.11

MVP

0.29

MPC

0.52

ClinPred

0.026

GERP RS

3.3

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.059

gMVP

0.16

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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