chr9-128166275-C-T

Variant names:

• chr9-128166275-C-T
• rs1350719452
• NM_001131016.2:c.2619G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001131016.2(CIZ1):​c.2619G>A​(p.Gln873Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 612,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 9-128166275-C-T is Benign according to our data. Variant chr9-128166275-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3663250.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.

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.2619G>A	p.Gln873Gln	synonymous	Exon 17 of 17	NP_001124488.1	Q9ULV3-1
	CIZ1	NM_001257975.2		c.2787G>A	p.Gln929Gln	synonymous	Exon 18 of 18	NP_001244904.1	F5H2X7
	CIZ1	NM_012127.3		c.2619G>A	p.Gln873Gln	synonymous	Exon 17 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.2619G>A	p.Gln873Gln	synonymous	Exon 17 of 17	ENSP00000362029.5	Q9ULV3-1
	CIZ1	ENST00000415526.5	TSL:1	c.2385G>A	p.Gln795Gln	synonymous	Exon 15 of 15	ENSP00000398011.1	H0Y5D5
	CIZ1	ENST00000372954.5	TSL:1	c.2379G>A	p.Gln793Gln	synonymous	Exon 17 of 17	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183746 AF XY: 0.0000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000370

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000129

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000653 AC: 4 AN: 612572 Hom.: 0 Cov.: 28 AF XY: 0.00000318 AC XY: 1 AN XY: 314752

African (AFR) AF: 0.00 AC: 0 AN: 14952

American (AMR) AF: 0.0000337 AC: 1 AN: 29662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12220

East Asian (EAS) AF: 0.00 AC: 0 AN: 12342

South Asian (SAS) AF: 0.0000152 AC: 1 AN: 65712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2808

European-Non Finnish (NFE) AF: 0.00000475 AC: 2 AN: 421496

Other (OTH) AF: 0.00 AC: 0 AN: 23658

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.4
DANN	Benign	0.92
PhyloP100		1.4

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: rs1350719452; hg19: chr9-130928554;