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GeneBe

9-128166354-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001131016.2(CIZ1):c.2540G>A(p.Arg847Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,561,462 control chromosomes in the GnomAD database, including 480 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 32 hom., cov: 32)
Exomes 𝑓: 0.023 ( 448 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

3
13

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.883
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0023836792).
BP6
Variant 9-128166354-C-T is Benign according to our data. Variant chr9-128166354-C-T is described in ClinVar as [Benign]. Clinvar id is 413837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128166354-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0184 (2807/152192) while in subpopulation NFE AF= 0.0258 (1754/67996). AF 95% confidence interval is 0.0248. There are 32 homozygotes in gnomad4. There are 1352 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2807 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CIZ1NM_001131016.2 linkuse as main transcriptc.2540G>A p.Arg847Gln missense_variant 17/17 ENST00000372938.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CIZ1ENST00000372938.10 linkuse as main transcriptc.2540G>A p.Arg847Gln missense_variant 17/171 NM_001131016.2 P2Q9ULV3-1

Frequencies

GnomAD3 genomes
AF:
0.0185
AC:
2808
AN:
152074
Hom.:
32
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00430
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.0174
Gnomad ASJ
AF:
0.0449
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.0130
Gnomad FIN
AF:
0.0316
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.0258
Gnomad OTH
AF:
0.0163
GnomAD3 exomes
AF:
0.0200
AC:
3336
AN:
166696
Hom.:
49
AF XY:
0.0200
AC XY:
1769
AN XY:
88452
show subpopulations
Gnomad AFR exome
AF:
0.00374
Gnomad AMR exome
AF:
0.0141
Gnomad ASJ exome
AF:
0.0452
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0142
Gnomad FIN exome
AF:
0.0270
Gnomad NFE exome
AF:
0.0253
Gnomad OTH exome
AF:
0.0250
GnomAD4 exome
AF:
0.0232
AC:
32695
AN:
1409270
Hom.:
448
Cov.:
33
AF XY:
0.0229
AC XY:
15944
AN XY:
695976
show subpopulations
Gnomad4 AFR exome
AF:
0.00396
Gnomad4 AMR exome
AF:
0.0141
Gnomad4 ASJ exome
AF:
0.0472
Gnomad4 EAS exome
AF:
0.0000815
Gnomad4 SAS exome
AF:
0.0138
Gnomad4 FIN exome
AF:
0.0280
Gnomad4 NFE exome
AF:
0.0247
Gnomad4 OTH exome
AF:
0.0234
GnomAD4 genome
AF:
0.0184
AC:
2807
AN:
152192
Hom.:
32
Cov.:
32
AF XY:
0.0182
AC XY:
1352
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.00429
Gnomad4 AMR
AF:
0.0173
Gnomad4 ASJ
AF:
0.0449
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0131
Gnomad4 FIN
AF:
0.0316
Gnomad4 NFE
AF:
0.0258
Gnomad4 OTH
AF:
0.0161
Alfa
AF:
0.0253
Hom.:
132
Bravo
AF:
0.0172
TwinsUK
AF:
0.0216
AC:
80
ALSPAC
AF:
0.0223
AC:
86
ESP6500AA
AF:
0.00460
AC:
20
ESP6500EA
AF:
0.0243
AC:
207
ExAC
AF:
0.0144
AC:
1669
Asia WGS
AF:
0.00347
AC:
13
AN:
3476

ClinVar

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

Submissions by phenotype

Dystonic disorder Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
21
DANN
Uncertain
1.0
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.45
N
LIST_S2
Uncertain
0.86
D;D;D;D;D;.;D;.;D;D
MetaRNN
Benign
0.0024
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.36
N;.;N;.;.;N;N;N;.;N
REVEL
Benign
0.034
Sift
Benign
0.061
T;.;T;.;.;T;T;T;.;T
Sift4G
Uncertain
0.038
D;D;D;D;T;D;D;D;D;D
Polyphen
0.12
B;.;P;.;.;P;P;P;P;.
Vest4
0.057
MPC
0.35
ClinPred
0.021
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.032
gMVP
0.51

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: rs11549260; hg19: chr9-130928633; COSMIC: COSV52974302; COSMIC: COSV52974302; API