Variant rs12334 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001131016.2(CIZ1):c.1733C>T(p.Ser578Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,591,550 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 154 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 132 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.42

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018073916).

BP6

Variant 9-128177651-G-A is Benign according to our data. Variant chr9-128177651-G-A is described in ClinVar as [Benign]. Clinvar id is 413839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIZ1	NM_001131016.2 linkuse as main transcript	c.1733C>T	p.Ser578Phe	missense_variant	10/17	ENST00000372938.10	NP_001124488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000372938.10 linkuse as main transcript	c.1733C>T	p.Ser578Phe	missense_variant	10/17	1	NM_001131016.2	ENSP00000362029	P2	Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3772

AN:

152138

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0862

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00668

AC:

1414

AN:

211726

Hom.:

AF XY:

0.00487

AC XY:

556

AN XY:

114116

show subpopulations

Gnomad AFR exome

AF:

0.0885

Gnomad AMR exome

AF:

0.00519

Gnomad ASJ exome

AF:

0.00759

Gnomad EAS exome

AF:

0.0000631

Gnomad SAS exome

AF:

0.0000377

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.00487

GnomAD4 exome

AF:

0.00263

AC:

3783

AN:

1439294

Hom.:

132

Cov.:

AF XY:

0.00231

AC XY:

1648

AN XY:

713814

show subpopulations

Gnomad4 AFR exome

AF:

0.0877

Gnomad4 AMR exome

AF:

0.00540

Gnomad4 ASJ exome

AF:

0.00726

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.000157

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.00550

GnomAD4 genome

AF:

0.0248

AC:

3782

AN:

152256

Hom.:

154

Cov.:

AF XY:

0.0239

AC XY:

1776

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0862

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.00565

Hom.:

Bravo

AF:

0.0283

ESP6500AA

AF:

0.0888

AC:

390

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00757

AC:

916

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

.;.;T;T;.;T;.;T;T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.91

D;D;D;D;D;.;D;.;D;D

MetaRNN

Benign

0.0018

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;.;.;.;.;.;.;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

N;.;N;.;.;N;N;N;.;N

REVEL

Benign

0.037

Sift

Uncertain

0.0020

D;.;D;.;.;D;D;D;.;D

Sift4G

Benign

0.081

T;D;D;D;D;D;D;D;D;D

Polyphen

0.93

P;.;P;.;.;P;P;P;P;.

Vest4

0.11

MVP

0.29

MPC

0.52

ClinPred

0.026

GERP RS

3.3

Varity_R

0.059

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over