9-128166354-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001131016.2(CIZ1):c.2540G>A(p.Arg847Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,561,462 control chromosomes in the GnomAD database, including 480 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 (★★).

Frequency

Genomes: 𝑓 0.018 ( 32 hom., cov: 32)

Exomes 𝑓: 0.023 ( 448 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.883

Publications

11 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=0.0023836792).

BP6

Variant 9-128166354-C-T is Benign according to our data. Variant chr9-128166354-C-T is described in ClinVar as Benign. ClinVar VariationId is 413837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0184 (2807/152192) while in subpopulation NFE AF = 0.0258 (1754/67996). AF 95% confidence interval is 0.0248. There are 32 homozygotes in GnomAd4. There are 1352 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2807 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIZ1	NM_001131016.2 link	c.2540G>A	p.Arg847Gln	missense_variant	Exon 17 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.2540G>A	p.Arg847Gln	missense_variant	Exon 17 of 17	1	NM_001131016.2	ENSP00000362029.5		Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2808

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.0449

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.0316

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0200

AC:

3336

AN:

166696

AF XY:

0.0200

show subpopulations

Gnomad AFR exome

AF:

0.00374

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0452

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0270

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0232

AC:

32695

AN:

1409270

Hom.:

448

Cov.:

AF XY:

0.0229

AC XY:

15944

AN XY:

695976

show subpopulations

African (AFR)

AF:

0.00396

AC:

128

AN:

32300

American (AMR)

AF:

0.0141

AC:

519

AN:

36724

Ashkenazi Jewish (ASJ)

AF:

0.0472

AC:

1187

AN:

25168

East Asian (EAS)

AF:

0.0000815

AC:

AN:

36800

South Asian (SAS)

AF:

0.0138

AC:

1105

AN:

79872

European-Finnish (FIN)

AF:

0.0280

AC:

1398

AN:

49968

Middle Eastern (MID)

AF:

0.0362

AC:

204

AN:

5634

European-Non Finnish (NFE)

AF:

0.0247

AC:

26787

AN:

1084434

Other (OTH)

AF:

0.0234

AC:

1364

AN:

58370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1687

3374

5060

6747

8434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1012

2024

3036

4048

5060

<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:

0.0184

AC:

2807

AN:

152192

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1352

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00429

AC:

178

AN:

41528

American (AMR)

AF:

0.0173

AC:

265

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0449

AC:

156

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.0131

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0316

AC:

335

AN:

10590

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0258

AC:

1754

AN:

67996

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

153

306

460

613

766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0239

Hom.:

233

Bravo

AF:

0.0172

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0223

AC:

ESP6500AA

AF:

0.00460

AC:

ESP6500EA

AF:

0.0243

AC:

207

ExAC

AF:

0.0144

AC:

1669

Asia WGS

AF:

0.00347

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dystonic disorder

Benign:1

Feb 02, 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

0.14

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

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

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.86

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

MetaRNN

Benign

0.0024

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

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

PhyloP100

0.88

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.36

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

REVEL

Benign

0.034

Sift

Benign

0.061

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

Sift4G

Uncertain

0.038

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

Polyphen

0.12

B;.;P;.;.;P;P;P;P;.

Vest4

0.057

MPC

0.35

ClinPred

0.021

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.032

gMVP

0.51

Mutation Taster

=99/1

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