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GeneBe

9-128166246-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001131016.2(CIZ1):c.2648G>A(p.Arg883Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,469,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.80
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.019570619).
BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CIZ1NM_001131016.2 linkuse as main transcriptc.2648G>A p.Arg883Gln missense_variant 17/17 ENST00000372938.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CIZ1ENST00000372938.10 linkuse as main transcriptc.2648G>A p.Arg883Gln missense_variant 17/171 NM_001131016.2 P2Q9ULV3-1

Frequencies

GnomAD3 genomes
AF:
0.0000561
AC:
8
AN:
142616
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000419
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000226
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000506
GnomAD3 exomes
AF:
0.0000323
AC:
5
AN:
154990
Hom.:
0
AF XY:
0.0000124
AC XY:
1
AN XY:
80822
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000824
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000147
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000157
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
20
AN:
1326876
Hom.:
0
Cov.:
33
AF XY:
0.0000108
AC XY:
7
AN XY:
647866
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000594
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000883
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000107
Gnomad4 OTH exome
AF:
0.0000560
GnomAD4 genome
AF:
0.0000561
AC:
8
AN:
142616
Hom.:
0
Cov.:
31
AF XY:
0.0000289
AC XY:
2
AN XY:
69116
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000419
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000226
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000506
Alfa
AF:
0.0000843
Hom.:
0
Bravo
AF:
0.0000982
ExAC
AF:
0.0000167
AC:
2

ClinVar

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

Submissions by phenotype

Dystonic disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJun 29, 2023In 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2171235). This variant has not been reported in the literature in individuals affected with CIZ1-related conditions. This variant is present in population databases (rs772580580, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 883 of the CIZ1 protein (p.Arg883Gln). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.89
DANN
Benign
0.88
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.83
T;T;T;T;T;.;T;.;T;T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.020
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.39
N;.;N;.;.;N;N;N;.;N
REVEL
Benign
0.015
Sift
Benign
0.37
T;.;T;.;.;T;T;T;.;T
Sift4G
Benign
0.70
T;T;T;T;T;T;T;T;T;T
Polyphen
0.043
B;.;B;.;.;B;B;B;B;.
Vest4
0.099
MutPred
0.089
.;.;.;.;.;.;.;Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);.;
MVP
0.48
MPC
0.31
ClinPred
0.014
T
GERP RS
-7.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.0094
gMVP
0.17

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: rs772580580; hg19: chr9-130928525; API