rs369660377

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_001131016.2(CIZ1):​c.2594G>T​(p.Arg865Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000354 in 1,412,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R865H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.95
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20118812).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CIZ1NM_001131016.2 linkc.2594G>T p.Arg865Leu missense_variant Exon 17 of 17 ENST00000372938.10 NP_001124488.1 Q9ULV3-1A0A024R885

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CIZ1ENST00000372938.10 linkc.2594G>T p.Arg865Leu missense_variant Exon 17 of 17 1 NM_001131016.2 ENSP00000362029.5 Q9ULV3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000354
AC:
5
AN:
1412858
Hom.:
0
Cov.:
33
AF XY:
0.00000430
AC XY:
3
AN XY:
697558
show subpopulations
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:
0.00000368
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.062
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.049
.;.;T;T;.;T;.;T;T;.
Eigen
Benign
-0.025
Eigen_PC
Benign
-0.085
FATHMM_MKL
Benign
0.58
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;.;D;.;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.20
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
.;.;.;.;.;.;.;L;L;.
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-2.1
N;.;N;D;.;N;N;N;.;N
REVEL
Benign
0.13
Sift
Uncertain
0.0080
D;.;D;D;.;D;D;D;.;D
Sift4G
Uncertain
0.026
D;D;D;D;D;D;D;D;D;D
Polyphen
0.94
P;.;D;.;.;D;P;D;D;.
Vest4
0.45
MutPred
0.12
.;.;.;.;.;.;.;Loss of MoRF binding (P = 0.0208);Loss of MoRF binding (P = 0.0208);.;
MVP
0.33
MPC
1.0
ClinPred
0.79
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130928579; API