Variant 9-128180748-C-T 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.655G>A(p.Ala219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,608,550 control chromosomes in the GnomAD database, including 1,457 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A219S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.054 ( 707 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 750 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

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=0.0010939837).

BP6

Variant 9-128180748-C-T is Benign according to our data. Variant chr9-128180748-C-T is described in ClinVar as [Benign]. Clinvar id is 413834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIZ1	NM_001131016.2 linkuse as main transcript	c.655G>A	p.Ala219Thr	missense_variant	6/17	ENST00000372938.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIZ1	ENST00000372938.10 linkuse as main transcript	c.655G>A	p.Ala219Thr	missense_variant	6/17	1	NM_001131016.2	P2	Q9ULV3-1

Frequencies

GnomAD3 genomes

AF:

0.0539

AC:

8194

AN:

152114

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0397

GnomAD3 exomes

AF:

0.0179

AC:

4397

AN:

245764

Hom.:

289

AF XY:

0.0157

AC XY:

2104

AN XY:

133670

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00494

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0310

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000829

Gnomad OTH exome

AF:

0.00969

GnomAD4 exome

AF:

0.00758

AC:

11043

AN:

1456318

Hom.:

750

Cov.:

AF XY:

0.00764

AC XY:

5537

AN XY:

725006

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.0120

Gnomad4 ASJ exome

AF:

0.00492

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0293

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000476

Gnomad4 OTH exome

AF:

0.0154

GnomAD4 genome

AF:

0.0539

AC:

8206

AN:

152232

Hom.:

707

Cov.:

AF XY:

0.0524

AC XY:

3899

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.0244

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0319

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.0397

Alfa

AF:

0.00349

Hom.:

Bravo

AF:

0.0620

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.179

AC:

787

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0211

AC:

2565

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Dystonic disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

Cadd

Benign

0.81

Dann

Benign

0.66

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.62

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

MetaRNN

Benign

0.0011

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.55

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

REVEL

Benign

0.052

Sift

Benign

0.44

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

Sift4G

Benign

0.47

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

Polyphen

0.0090

B;.;B;.;.;B;B;B;B;.;.

Vest4

0.050

MPC

0.26

ClinPred

0.0035

GERP RS

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.024

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

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