NM_001131016.2:c.1957A>C

Variant names:

• chr9-128170094-T-G
• rs45611034
• NM_001131016.2:c.1957A>C

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.1957A>C​(p.Arg653Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,605,114 control chromosomes in the GnomAD database, including 462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (36 hom., cov: 33)
  • Exomes 𝑓: 0.022 (426 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16
• Publications: 4 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=-0.72).
• BP6: Variant 9-128170094-T-G is Benign according to our data. Variant chr9-128170094-T-G is described in ClinVar as Benign. ClinVar VariationId is 413832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.02 (2870/143754) while in subpopulation AMR AF = 0.0286 (381/13318). AF 95% confidence interval is 0.0264. There are 36 homozygotes in GnomAd4. There are 1373 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2870 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.1957A>C	p.Arg653Arg	synonymous	Exon 12 of 17	NP_001124488.1	Q9ULV3-1
	CIZ1	NM_001257975.2		c.2047A>C	p.Arg683Arg	synonymous	Exon 12 of 18	NP_001244904.1	F5H2X7
	CIZ1	NM_012127.3		c.1957A>C	p.Arg653Arg	synonymous	Exon 12 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.1957A>C	p.Arg653Arg	synonymous	Exon 12 of 17	ENSP00000362029.5	Q9ULV3-1
	CIZ1	ENST00000415526.5	TSL:1	c.1723A>C	p.Arg575Arg	synonymous	Exon 10 of 15	ENSP00000398011.1	H0Y5D5
	CIZ1	ENST00000372954.5	TSL:1	c.1717A>C	p.Arg573Arg	synonymous	Exon 12 of 17	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 2871 AN: 143632 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.00436

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0379

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.0762

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0279

GnomAD2 exomes AF: 0.0189 AC: 4677 AN: 248022 AF XY: 0.0196

Gnomad AFR exome AF: 0.00388

Gnomad AMR exome AF: 0.0166

Gnomad ASJ exome AF: 0.0360

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.0259

Gnomad OTH exome AF: 0.0253

GnomAD4 exome AF: 0.0216 AC: 31592 AN: 1461360 Hom.: 426 Cov.: 32 AF XY: 0.0217 AC XY: 15746 AN XY: 727022

African (AFR) AF: 0.00454 AC: 152 AN: 33464

American (AMR) AF: 0.0164 AC: 729 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.0365 AC: 954 AN: 26128

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

South Asian (SAS) AF: 0.0111 AC: 959 AN: 86240

European-Finnish (FIN) AF: 0.0145 AC: 774 AN: 53416

Middle Eastern (MID) AF: 0.0526 AC: 303 AN: 5764

European-Non Finnish (NFE) AF: 0.0237 AC: 26355 AN: 1111718

Other (OTH) AF: 0.0226 AC: 1364 AN: 60376

GnomAD4 genome AF: 0.0200 AC: 2870 AN: 143754 Hom.: 36 Cov.: 33 AF XY: 0.0197 AC XY: 1373 AN XY: 69638

African (AFR) AF: 0.00435 AC: 179 AN: 41190

American (AMR) AF: 0.0286 AC: 381 AN: 13318

Ashkenazi Jewish (ASJ) AF: 0.0379 AC: 127 AN: 3348

East Asian (EAS) AF: 0.000203 AC: 1 AN: 4916

South Asian (SAS) AF: 0.0129 AC: 54 AN: 4186

European-Finnish (FIN) AF: 0.0162 AC: 157 AN: 9710

Middle Eastern (MID) AF: 0.0775 AC: 22 AN: 284

European-Non Finnish (NFE) AF: 0.0275 AC: 1759 AN: 64032

Other (OTH) AF: 0.0281 AC: 54 AN: 1924

Alfa AF: 0.0229 Hom.: 75

Bravo AF: 0.0191

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.0309

EpiControl AF: 0.0303

ClinVar

ClinVar submissions as Germline

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	-0.72
CADD	Benign	9.3
DANN	Benign	0.64
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs45611034; hg19: chr9-130932373;