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GeneBe

9-128166220-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001131016.2(CIZ1):c.2674C>T(p.Arg892Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,341,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

3
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.33584148).
BS2
High AC in GnomAdExome at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CIZ1NM_001131016.2 linkuse as main transcriptc.2674C>T p.Arg892Cys missense_variant 17/17 ENST00000372938.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CIZ1ENST00000372938.10 linkuse as main transcriptc.2674C>T p.Arg892Cys missense_variant 17/171 NM_001131016.2 P2Q9ULV3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000371
AC:
5
AN:
134680
Hom.:
0
AF XY:
0.0000144
AC XY:
1
AN XY:
69382
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000143
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000789
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000184
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000119
AC:
16
AN:
1341042
Hom.:
0
Cov.:
33
AF XY:
0.0000107
AC XY:
7
AN XY:
653296
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000962
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000275
Gnomad4 SAS exome
AF:
0.0000142
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000958
Gnomad4 OTH exome
AF:
0.0000181
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000756

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 testingInvitaeJul 05, 2023This variant has not been reported in the literature in individuals affected with CIZ1-related conditions. 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 892 of the CIZ1 protein (p.Arg892Cys). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Benign
-0.0017
T
BayesDel_noAF
Benign
-0.24
Cadd
Pathogenic
29
Dann
Pathogenic
1.0
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;.;D;.;D;D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.34
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.73
T
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.6
D;.;D;.;.;D;D;D;.;D
REVEL
Benign
0.21
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
0.59
MVP
0.41
MPC
1.1
ClinPred
0.82
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.40
gMVP
0.44

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: rs1444613490; hg19: chr9-130928499; API