NM_001131016.2:c.396C>T

Variant names:

• chr9-128185739-G-A
• rs45545033
• NM_001131016.2:c.396C>T

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.396C>T​(p.Leu132Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,613,414 control chromosomes in the GnomAD database, including 578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (299 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (279 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.365
• Publications: 6 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=-0.71).
• BP6: Variant 9-128185739-G-A is Benign according to our data. Variant chr9-128185739-G-A is described in ClinVar as Benign. ClinVar VariationId is 413833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.365 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	NM_001131016.2	MANE Select	c.396C>T	p.Leu132Leu	synonymous	Exon 5 of 17	NP_001124488.1
	CIZ1	NM_001257975.2		c.486C>T	p.Leu162Leu	synonymous	Exon 5 of 18	NP_001244904.1
	CIZ1	NM_012127.3		c.396C>T	p.Leu132Leu	synonymous	Exon 5 of 17	NP_036259.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	ENST00000372938.10	TSL:1 MANE Select	c.396C>T	p.Leu132Leu	synonymous	Exon 5 of 17	ENSP00000362029.5
	CIZ1	ENST00000415526.5	TSL:1	c.177C>T	p.Leu59Leu	synonymous	Exon 3 of 15	ENSP00000398011.1
	CIZ1	ENST00000372954.5	TSL:1	c.324C>T	p.Leu108Leu	synonymous	Exon 4 of 17	ENSP00000362045.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5265 AN: 152088 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.00915 AC: 2287 AN: 249954 AF XY: 0.00655

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.00581

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000416

Gnomad OTH exome AF: 0.00443

GnomAD4 exome AF: 0.00358 AC: 5234 AN: 1461208 Hom.: 279 Cov.: 33 AF XY: 0.00300 AC XY: 2183 AN XY: 726906

African (AFR) AF: 0.124 AC: 4147 AN: 33458

American (AMR) AF: 0.00647 AC: 289 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26076

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5764

European-Non Finnish (NFE) AF: 0.000227 AC: 252 AN: 1111710

Other (OTH) AF: 0.00805 AC: 486 AN: 60362

GnomAD4 genome AF: 0.0347 AC: 5284 AN: 152206 Hom.: 299 Cov.: 32 AF XY: 0.0338 AC XY: 2515 AN XY: 74424

African (AFR) AF: 0.120 AC: 4991 AN: 41514

American (AMR) AF: 0.0137 AC: 209 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 67998

Other (OTH) AF: 0.0204 AC: 43 AN: 2112

Alfa AF: 0.0325 Hom.: 235

Bravo AF: 0.0391

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dystonic disorder Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.7
DANN	Benign	0.75
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs45545033; hg19: chr9-130948018;