9-128180748-C-T

Variant names:

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.655G>A(p.Ala219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,608,550 control chromosomes in the GnomAD database, including 1,457 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A219S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.054 ( 707 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 750 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.06

Publications

10 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=0.0010939837).

BP6

Variant 9-128180748-C-T is Benign according to our data. Variant chr9-128180748-C-T is described in ClinVar as Benign. ClinVar VariationId is 413834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIZ1	NM_001131016.2 link	c.655G>A	p.Ala219Thr	missense_variant	Exon 6 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.655G>A	p.Ala219Thr	missense_variant	Exon 6 of 17	1	NM_001131016.2	ENSP00000362029.5

Frequencies

GnomAD3 genomes

AF:

0.0539

AC:

8194

AN:

152114

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0397

GnomAD2 exomes

AF:

0.0179

AC:

4397

AN:

245764

AF XY:

0.0157

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00494

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000829

Gnomad OTH exome

AF:

0.00969

GnomAD4 exome

AF:

0.00758

AC:

11043

AN:

1456318

Hom.:

750

Cov.:

AF XY:

0.00764

AC XY:

5537

AN XY:

725006

show subpopulations

African (AFR)

AF:

0.193

AC:

6332

AN:

32820

American (AMR)

AF:

0.0120

AC:

515

AN:

42794

Ashkenazi Jewish (ASJ)

AF:

0.00492

AC:

128

AN:

26026

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39684

South Asian (SAS)

AF:

0.0293

AC:

2519

AN:

85994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52914

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.000476

AC:

529

AN:

1110250

Other (OTH)

AF:

0.0154

AC:

924

AN:

60152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

465

931

1396

1862

2327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<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:

0.0539

AC:

8206

AN:

152232

Hom.:

707

Cov.:

AF XY:

0.0524

AC XY:

3899

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.181

AC:

7527

AN:

41502

American (AMR)

AF:

0.0244

AC:

373

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0319

AC:

154

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68014

Other (OTH)

AF:

0.0397

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

343

687

1030

1374

1717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0163

Hom.:

457

Bravo

AF:

0.0620

TwinsUK

AF:

0.000539

AC:

ESP6500AA

AF:

0.179

AC:

787

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0211

AC:

2565

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 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 27, 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

0.075

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.81

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

LIST_S2

Benign

0.62

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

MetaRNN

Benign

0.0011

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

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

PhyloP100

-1.1

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.55

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

Sift

Benign

0.44

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

Sift4G

Benign

0.47

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

Vest4

0.050

ClinPred

0.0035

GERP RS

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.024

Mutation Taster

=100/0

polymorphism (auto)

(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

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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