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GeneBe

9-128166331-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001131016.2(CIZ1):c.2563G>A(p.Ala855Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000849 in 1,413,186 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A855S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

2
5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1571882).
BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CIZ1NM_001131016.2 linkuse as main transcriptc.2563G>A p.Ala855Thr missense_variant 17/17 ENST00000372938.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CIZ1ENST00000372938.10 linkuse as main transcriptc.2563G>A p.Ala855Thr missense_variant 17/171 NM_001131016.2 P2Q9ULV3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000233
AC:
4
AN:
171876
Hom.:
0
AF XY:
0.0000438
AC XY:
4
AN XY:
91320
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000384
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000843
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000144
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000849
AC:
12
AN:
1413186
Hom.:
0
Cov.:
33
AF XY:
0.0000100
AC XY:
7
AN XY:
698192
show subpopulations
Gnomad4 AFR exome
AF:
0.0000308
Gnomad4 AMR exome
AF:
0.0000269
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000249
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000736
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000170
AC:
2

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 GeneticsDec 17, 2023The c.2563G>A (p.A855T) alteration is located in exon 17 (coding exon 16) of the CIZ1 gene. This alteration results from a G to A substitution at nucleotide position 2563, causing the alanine (A) at amino acid position 855 to be replaced by a threonine (T). 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
Pathogenic
0.70
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
27
DANN
Uncertain
1.0
Eigen
Uncertain
0.30
Eigen_PC
Benign
0.22
FATHMM_MKL
Benign
0.61
D
LIST_S2
Uncertain
0.92
D;D;D;D;D;.;D;.;D;D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.16
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
1.0
D;N;N;N;N;N;N;N;N;N
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.5
N;.;N;.;.;N;N;N;.;N
REVEL
Benign
0.11
Sift
Pathogenic
0.0
D;.;D;.;.;D;D;D;.;D
Sift4G
Uncertain
0.011
D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;D;.;.;D;D;D;D;.
Vest4
0.48
MutPred
0.27
.;.;.;.;.;.;.;Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);.;
MVP
0.35
MPC
0.93
ClinPred
0.39
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.27
gMVP
0.37

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: rs755157078; hg19: chr9-130928610; API