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GeneBe

9-128166213-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001131016.2(CIZ1):c.2681C>T(p.Thr894Ile) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CIZ1
NM_001131016.2 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.605
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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09903219).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CIZ1NM_001131016.2 linkuse as main transcriptc.2681C>T p.Thr894Ile missense_variant 17/17 ENST00000372938.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CIZ1ENST00000372938.10 linkuse as main transcriptc.2681C>T p.Thr894Ile missense_variant 17/171 NM_001131016.2 P2Q9ULV3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1324068
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
644062
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 16, 2021The c.2681C>T (p.T894I) alteration is located in exon 17 (coding exon 16) of the CIZ1 gene. This alteration results from a C to T substitution at nucleotide position 2681, causing the threonine (T) at amino acid position 894 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
18
DANN
Uncertain
0.99
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.13
N
LIST_S2
Uncertain
0.90
D;D;D;D;D;.;D;.;D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.099
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.75
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.4
N;.;N;.;.;N;N;N;.;N
REVEL
Benign
0.16
Sift
Uncertain
0.0010
D;.;D;.;.;D;D;D;.;D
Sift4G
Uncertain
0.012
D;D;D;D;D;D;D;D;D;D
Polyphen
0.96
D;.;P;.;.;P;D;D;D;.
Vest4
0.16
MutPred
0.23
.;.;.;.;.;.;.;Loss of phosphorylation at T894 (P = 9e-04);Loss of phosphorylation at T894 (P = 9e-04);.;
MVP
0.14
MPC
0.63
ClinPred
0.28
T
GERP RS
-0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.091
gMVP
0.39

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: rs1829390555; hg19: chr9-130928492; API