Genetic Variant NM_001131016.2:c.2643G>A (chr9-128166251-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001131016.2(CIZ1):c.2643G>A(p.Thr881Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000769 in 1,470,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

CIZ1
NM_001131016.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.04

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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 9-128166251-C-T is Benign according to our data. Variant chr9-128166251-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2851915.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BS2

High AC in GnomAd4 at 9 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	UniProt
CIZ1	NM_001131016.2	MANE Select	c.2643G>A	p.Thr881Thr	synonymous	Exon 17 of 17	NP_001124488.1	Q9ULV3-1
CIZ1	NM_001257975.2		c.2811G>A	p.Thr937Thr	synonymous	Exon 18 of 18	NP_001244904.1	F5H2X7
CIZ1	NM_012127.3		c.2643G>A	p.Thr881Thr	synonymous	Exon 17 of 17	NP_036259.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIZ1	ENST00000372938.10	TSL:1 MANE Select	c.2643G>A	p.Thr881Thr	synonymous	Exon 17 of 17	ENSP00000362029.5	Q9ULV3-1
CIZ1	ENST00000415526.5	TSL:1	c.2409G>A	p.Thr803Thr	synonymous	Exon 15 of 15	ENSP00000398011.1	H0Y5D5
CIZ1	ENST00000372954.5	TSL:1	c.2403G>A	p.Thr801Thr	synonymous	Exon 17 of 17	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes

AF:

0.0000620

AC:

AN:

145210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000683

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:

0.000106

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000607

AC:

AN:

164676

AF XY:

0.00

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:

0.0000146

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000785

AC:

104

AN:

1324836

Hom.:

Cov.:

AF XY:

0.0000663

AC XY:

AN XY:

648338

show subpopulations

African (AFR)

AF:

0.0000328

AC:

AN:

30464

American (AMR)

AF:

0.00

AC:

AN:

34088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21074

East Asian (EAS)

AF:

0.00

AC:

AN:

33190

South Asian (SAS)

AF:

0.00

AC:

AN:

75162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4436

European-Non Finnish (NFE)

AF:

0.0000972

AC:

100

AN:

1028454

Other (OTH)

AF:

0.0000565

AC:

AN:

53066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000620

AC:

AN:

145210

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

70604

show subpopulations

African (AFR)

AF:

0.0000252

AC:

AN:

39706

American (AMR)

AF:

0.0000683

AC:

AN:

14642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3386

East Asian (EAS)

AF:

0.00

AC:

AN:

4582

South Asian (SAS)

AF:

0.00

AC:

AN:

4184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000106

AC:

AN:

66128

Other (OTH)

AF:

0.00

AC:

AN:

1998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.0000323

Hom.:

Bravo

AF:

0.0000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.4

(source)

DANN

Benign

0.88

PhyloP100

-1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over