rs369660377

Variant names:

• chr9-128166300-C-A
• rs369660377
• NM_001131016.2:c.2594G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-128166300-C-A
• chr9-128166300-C-G
• chr9-128166300-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_001131016.2(CIZ1):​c.2594G>T​(p.Arg865Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000354 in 1,412,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R865H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CIZ1 NM_001131016.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20118812).
• BS2: High AC in GnomAdExome4 at 5 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.2594G>T	p.Arg865Leu	missense	Exon 17 of 17	NP_001124488.1	Q9ULV3-1
	CIZ1	NM_001257975.2		c.2762G>T	p.Arg921Leu	missense	Exon 18 of 18	NP_001244904.1	F5H2X7
	CIZ1	NM_012127.3		c.2594G>T	p.Arg865Leu	missense	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.2594G>T	p.Arg865Leu	missense	Exon 17 of 17	ENSP00000362029.5	Q9ULV3-1
	CIZ1	ENST00000415526.5	TSL:1	c.2360G>T	p.Arg787Leu	missense	Exon 15 of 15	ENSP00000398011.1	H0Y5D5
	CIZ1	ENST00000372954.5	TSL:1	c.2354G>T	p.Arg785Leu	missense	Exon 17 of 17	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000354 AC: 5 AN: 1412858 Hom.: 0 Cov.: 33 AF XY: 0.00000430 AC XY: 3 AN XY: 697558

African (AFR) AF: 0.00 AC: 0 AN: 32620

American (AMR) AF: 0.00 AC: 0 AN: 37428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25134

East Asian (EAS) AF: 0.00 AC: 0 AN: 37500

South Asian (SAS) AF: 0.00 AC: 0 AN: 80220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5332

European-Non Finnish (NFE) AF: 0.00000368 AC: 4 AN: 1085642

Other (OTH) AF: 0.0000171 AC: 1 AN: 58496

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.026	D
Polyphen		0.94	P
Vest4		0.45
MutPred		0.12		Loss of MoRF binding (P = 0.0208)
MVP		0.33
MPC		1.0
ClinPred		0.79	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.40
Mutation Taster		=94/6	polymorphism

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: rs369660377; hg19: chr9-130928579;