9-128179037-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001131016.2(CIZ1):c.1170G>T(p.Gln390His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00693 in 1,613,994 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 34 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.68

Publications

4 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034489334).

BP6

Variant 9-128179037-C-A is Benign according to our data. Variant chr9-128179037-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 240851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 785 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131016.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CIZ1	NM_001131016.2	MANE Select	c.1170G>T	p.Gln390His	missense	Exon 8 of 17	NP_001124488.1
CIZ1	NM_001257975.2		c.1260G>T	p.Gln420His	missense	Exon 8 of 18	NP_001244904.1
CIZ1	NM_012127.3		c.1170G>T	p.Gln390His	missense	Exon 8 of 17	NP_036259.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CIZ1	ENST00000372938.10	TSL:1 MANE Select	c.1170G>T	p.Gln390His	missense	Exon 8 of 17	ENSP00000362029.5
CIZ1	ENST00000415526.5	TSL:1	c.936G>T	p.Gln312His	missense	Exon 6 of 15	ENSP00000398011.1
CIZ1	ENST00000372954.5	TSL:1	c.1062+36G>T		intron	N/A	ENSP00000362045.1

Frequencies

GnomAD3 genomes

AF:

0.00516

AC:

785

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00546

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00889

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00428

AC:

1064

AN:

248812

AF XY:

0.00431

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.000698

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00422

Gnomad NFE exome

AF:

0.00751

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00712

AC:

10402

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

5068

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33468

American (AMR)

AF:

0.00242

AC:

108

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.000498

AC:

AN:

26114

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00392

AC:

209

AN:

53384

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00873

AC:

9703

AN:

1111914

Other (OTH)

AF:

0.00536

AC:

324

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

731

1462

2192

2923

3654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.00515

AC:

785

AN:

152342

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

355

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41582

American (AMR)

AF:

0.00281

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00546

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00889

AC:

605

AN:

68018

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00687

Hom.:

Bravo

AF:

0.00505

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.00415

AC:

504

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00736

EpiControl

AF:

0.00842

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

CIZ1-related disorder (1)

Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.58

M_CAP

Benign

0.0047

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

1.7

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

REVEL

Benign

0.018

Sift

Uncertain

0.010

Sift4G

Uncertain

0.033

Polyphen

0.61

Vest4

0.20

MutPred

0.21

Loss of helix (P = 0.0444)

MVP

0.38

MPC

0.26

ClinPred

0.0032

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.19

Mutation Taster

=94/6

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

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over