NM_001131016.2:c.1227C>A

Variant names:

• chr9-128178980-G-T
• rs45559035
• NM_001131016.2:c.1227C>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.1227C>A​(p.Pro409Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00714 in 1,613,508 control chromosomes in the GnomAD database, including 394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (354 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -7.87
• 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=-0.84).
• BP6: Variant 9-128178980-G-T is Benign according to our data. Variant chr9-128178980-G-T is described in ClinVar as Benign. ClinVar VariationId is 413831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.87 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0784 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.1227C>A	p.Pro409Pro	synonymous	Exon 8 of 17	NP_001124488.1	Q9ULV3-1
	CIZ1	NM_001257975.2		c.1317C>A	p.Pro439Pro	synonymous	Exon 8 of 18	NP_001244904.1	F5H2X7
	CIZ1	NM_012127.3		c.1227C>A	p.Pro409Pro	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.1227C>A	p.Pro409Pro	synonymous	Exon 8 of 17	ENSP00000362029.5	Q9ULV3-1
	CIZ1	ENST00000415526.5	TSL:1	c.993C>A	p.Pro331Pro	synonymous	Exon 6 of 15	ENSP00000398011.1	H0Y5D5
	CIZ1	ENST00000372954.5	TSL:1	c.1063-76C>A		intron	N/A	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes AF: 0.00785 AC: 1190 AN: 151602 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000919

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.0372

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000987

Gnomad OTH AF: 0.00912

GnomAD2 exomes AF: 0.0154 AC: 3848 AN: 249704 AF XY: 0.0159

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00259

Gnomad EAS exome AF: 0.0894

Gnomad FIN exome AF: 0.0381

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.0155

GnomAD4 exome AF: 0.00706 AC: 10324 AN: 1461786 Hom.: 354 Cov.: 34 AF XY: 0.00775 AC XY: 5639 AN XY: 727194

African (AFR) AF: 0.000478 AC: 16 AN: 33478

American (AMR) AF: 0.000224 AC: 10 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 50 AN: 26126

East Asian (EAS) AF: 0.107 AC: 4228 AN: 39698

South Asian (SAS) AF: 0.0309 AC: 2662 AN: 86236

European-Finnish (FIN) AF: 0.0360 AC: 1920 AN: 53400

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.000701 AC: 780 AN: 1111972

Other (OTH) AF: 0.0106 AC: 641 AN: 60388

GnomAD4 genome AF: 0.00788 AC: 1195 AN: 151722 Hom.: 40 Cov.: 33 AF XY: 0.0103 AC XY: 763 AN XY: 74162

African (AFR) AF: 0.00109 AC: 45 AN: 41378

American (AMR) AF: 0.000918 AC: 14 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3464

East Asian (EAS) AF: 0.0850 AC: 437 AN: 5144

South Asian (SAS) AF: 0.0375 AC: 180 AN: 4802

European-Finnish (FIN) AF: 0.0400 AC: 421 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000988 AC: 67 AN: 67842

Other (OTH) AF: 0.0109 AC: 23 AN: 2106

Alfa AF: 0.00156 Hom.: 1

Bravo AF: 0.00452

EpiCase AF: 0.000763

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	-0.84
CADD	Benign	0.55
DANN	Benign	0.28
PhyloP100		-7.9
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: rs45559035; hg19: chr9-130941259;