dbSNP rs45611034: CIZ1:p.Arg653Trp (chr9-128170094-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001131016.2(CIZ1):c.1957A>T(p.Arg653Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,442 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. Synonymous variant affecting the same amino acid position (i.e. R653R) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

0 publications found

Variant links:

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

CIZ1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1701011).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIZ1	NM_001131016.2	MANE Select	c.1957A>T	p.Arg653Trp	missense	Exon 12 of 17	NP_001124488.1	Q9ULV3-1
CIZ1	NM_001257975.2		c.2047A>T	p.Arg683Trp	missense	Exon 12 of 18	NP_001244904.1	F5H2X7
CIZ1	NM_012127.3		c.1957A>T	p.Arg653Trp	missense	Exon 12 of 17	NP_036259.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CIZ1	ENST00000372938.10	TSL:1 MANE Select	c.1957A>T	p.Arg653Trp	missense	Exon 12 of 17	ENSP00000362029.5	Q9ULV3-1
CIZ1	ENST00000415526.5	TSL:1	c.1723A>T	p.Arg575Trp	missense	Exon 10 of 15	ENSP00000398011.1	H0Y5D5
CIZ1	ENST00000372954.5	TSL:1	c.1717A>T	p.Arg573Trp	missense	Exon 12 of 17	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111782

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

-0.073

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.018

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

1.2

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.068

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.40

MutPred

0.24

Loss of disorder (P = 0.0167)

MVP

0.34

MPC

0.91

ClinPred

0.95

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.33

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over