9-128166207-A-G

Variant summary

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

The NM_001131016.2(CIZ1):​c.2687T>C​(p.Leu896Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CIZ1
NM_001131016.2 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14
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]

Genome browser will be placed here

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=0.13178575).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CIZ1NM_001131016.2 linkc.2687T>C p.Leu896Pro missense_variant Exon 17 of 17 ENST00000372938.10 NP_001124488.1 Q9ULV3-1A0A024R885

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CIZ1ENST00000372938.10 linkc.2687T>C p.Leu896Pro missense_variant Exon 17 of 17 1 NM_001131016.2 ENSP00000362029.5 Q9ULV3-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
124646
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1174418
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
567764
Gnomad4 AFR exome
AF:
0.00
AC:
0
AN:
26022
Gnomad4 AMR exome
AF:
0.00
AC:
0
AN:
23712
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
14768
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
22280
Gnomad4 SAS exome
AF:
0.00
AC:
0
AN:
66824
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
34030
Gnomad4 NFE exome
AF:
0.00
AC:
0
AN:
939412
Gnomad4 Remaining exome
AF:
0.00
AC:
0
AN:
44168
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000855
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Dystonic disorder Uncertain:1
Jan 11, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with CIZ1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 896 of the CIZ1 protein (p.Leu896Pro). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Uncertain
0.030
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.049
.;.;T;T;.;T;.;T;T;.
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.87
D;D;D;D;D;.;D;.;D;D
M_CAP
Uncertain
0.091
D
MetaRNN
Benign
0.13
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
1.1
.;.;.;.;.;.;.;L;L;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.5
D;.;D;.;.;D;D;D;.;D
REVEL
Benign
0.18
Sift
Pathogenic
0.0
D;.;D;.;.;D;D;D;.;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;D;.;.;D;D;D;D;.
Vest4
0.47
MutPred
0.21
.;.;.;.;.;.;.;Loss of stability (P = 0.001);Loss of stability (P = 0.001);.;
MVP
0.27
MPC
1.2
ClinPred
0.92
D
GERP RS
3.8
Varity_R
0.62
gMVP
0.61
Mutation Taster
=84/16
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

Publications

LitVar

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

Other links and lift over

dbSNP: rs757332837; hg19: chr9-130928486; API