rs45536439

Variant names:

• chr9-128179172-C-T
• rs45536439
• NM_001131016.2:c.1035G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-128179172-C-T
• chr9-128179172-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001131016.2(CIZ1):​c.1035G>A​(p.Ala345Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00778 in 1,613,952 control chromosomes in the GnomAD database, including 662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (344 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (318 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -5.47
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 9-128179172-C-T is Benign according to our data. Variant chr9-128179172-C-T is described in ClinVar as Benign. ClinVar VariationId is 413836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	NM_001131016.2	MANE Select	c.1035G>A	p.Ala345Ala	synonymous	Exon 8 of 17	NP_001124488.1	Q9ULV3-1
	CIZ1	NM_001257975.2		c.1125G>A	p.Ala375Ala	synonymous	Exon 8 of 18	NP_001244904.1	F5H2X7
	CIZ1	NM_012127.3		c.1035G>A	p.Ala345Ala	synonymous	Exon 8 of 17	NP_036259.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	ENST00000372938.10	TSL:1 MANE Select	c.1035G>A	p.Ala345Ala	synonymous	Exon 8 of 17	ENSP00000362029.5	Q9ULV3-1
	CIZ1	ENST00000415526.5	TSL:1	c.801G>A	p.Ala267Ala	synonymous	Exon 6 of 15	ENSP00000398011.1	H0Y5D5
	CIZ1	ENST00000372954.5	TSL:1	c.963G>A	p.Ala321Ala	synonymous	Exon 7 of 17	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5765 AN: 152070 Hom.: 342 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.0106 AC: 2666 AN: 250376 AF XY: 0.00783

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.00920

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000973

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00463 AC: 6771 AN: 1461764 Hom.: 318 Cov.: 34 AF XY: 0.00403 AC XY: 2933 AN XY: 727188

African (AFR) AF: 0.132 AC: 4403 AN: 33478

American (AMR) AF: 0.00973 AC: 435 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86256

European-Finnish (FIN) AF: 0.000806 AC: 43 AN: 53344

Middle Eastern (MID) AF: 0.00624 AC: 36 AN: 5766

European-Non Finnish (NFE) AF: 0.00115 AC: 1281 AN: 1111982

Other (OTH) AF: 0.00894 AC: 540 AN: 60386

GnomAD4 genome AF: 0.0380 AC: 5789 AN: 152188 Hom.: 344 Cov.: 33 AF XY: 0.0374 AC XY: 2786 AN XY: 74400

African (AFR) AF: 0.128 AC: 5331 AN: 41498

American (AMR) AF: 0.0201 AC: 307 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00129 AC: 88 AN: 68006

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.0179 Hom.: 91

Bravo AF: 0.0427

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CIZ1-related disorder (1)
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.2
DANN	Benign	0.63
PhyloP100		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45536439; hg19: chr9-130941451;