chr9-128169142-G-A

Variant names:

• chr9-128169142-G-A
• rs41276236
• NM_001131016.2:c.2205C>T
• CIZ1 p.Asp735Asp

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001131016.2(CIZ1):​c.2205C>T​(p.Asp735Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,614,016 control chromosomes in the GnomAD database, including 383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (21 hom., cov: 32)
  • Exomes 𝑓: 0.021 (362 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.506
• Publications: 7 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=-0.73).
• BP6: Variant 9-128169142-G-A is Benign according to our data. Variant chr9-128169142-G-A is described in ClinVar as Benign. ClinVar VariationId is 240852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.506 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0142 (2159/152182) while in subpopulation NFE AF = 0.0218 (1481/68006). AF 95% confidence interval is 0.0209. There are 21 homozygotes in GnomAd4. There are 987 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2159 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	NM_001131016.2	MANE Select	c.2205C>T	p.Asp735Asp	synonymous	Exon 14 of 17	NP_001124488.1	Q9ULV3-1
	CIZ1	NM_001257975.2		c.2373C>T	p.Asp791Asp	synonymous	Exon 15 of 18	NP_001244904.1	F5H2X7
	CIZ1	NM_012127.3		c.2205C>T	p.Asp735Asp	synonymous	Exon 14 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.2205C>T	p.Asp735Asp	synonymous	Exon 14 of 17	ENSP00000362029.5	Q9ULV3-1
	CIZ1	ENST00000415526.5	TSL:1	c.1971C>T	p.Asp657Asp	synonymous	Exon 12 of 15	ENSP00000398011.1	H0Y5D5
	CIZ1	ENST00000372954.5	TSL:1	c.1965C>T	p.Asp655Asp	synonymous	Exon 14 of 17	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2161 AN: 152064 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00418

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.0138 AC: 3425 AN: 249064 AF XY: 0.0137

Gnomad AFR exome AF: 0.00369

Gnomad AMR exome AF: 0.0114

Gnomad ASJ exome AF: 0.0180

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0146

Gnomad NFE exome AF: 0.0207

Gnomad OTH exome AF: 0.0153

GnomAD4 exome AF: 0.0210 AC: 30757 AN: 1461834 Hom.: 362 Cov.: 32 AF XY: 0.0204 AC XY: 14811 AN XY: 727222

African (AFR) AF: 0.00314 AC: 105 AN: 33480

American (AMR) AF: 0.0117 AC: 525 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0165 AC: 431 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00246 AC: 212 AN: 86258

European-Finnish (FIN) AF: 0.0159 AC: 851 AN: 53410

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5768

European-Non Finnish (NFE) AF: 0.0246 AC: 27368 AN: 1111966

Other (OTH) AF: 0.0201 AC: 1214 AN: 60392

GnomAD4 genome AF: 0.0142 AC: 2159 AN: 152182 Hom.: 21 Cov.: 32 AF XY: 0.0133 AC XY: 987 AN XY: 74418

African (AFR) AF: 0.00417 AC: 173 AN: 41510

American (AMR) AF: 0.0134 AC: 205 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

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

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10586

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0218 AC: 1481 AN: 68006

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.0193 Hom.: 60

Bravo AF: 0.0139

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0206

EpiControl AF: 0.0236

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.51
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41276236;

hg19: chr9-130931421;

COSMIC: COSV108066098;

COSMIC: COSV108066098;