Variant 9-128166324-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001131016.2(CIZ1):c.2570C>A(p.Thr857Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000424 in 1,415,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

CIZ1
NM_001131016.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

CIZ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1875551).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIZ1	NM_001131016.2 linkuse as main transcript	c.2570C>A	p.Thr857Lys	missense_variant	17/17	ENST00000372938.10	NP_001124488.1	Q9ULV3-1A0A024R885

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000372938.10 linkuse as main transcript	c.2570C>A	p.Thr857Lys	missense_variant	17/17	1	NM_001131016.2	ENSP00000362029.5		Q9ULV3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000424

AC:

AN:

1415966

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

699772

show subpopulations

Gnomad4 AFR exome

AF:

0.000184

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000843

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.2570C>A (p.T857K) alteration is located in exon 17 (coding exon 16) of the CIZ1 gene. This alteration results from a C to A substitution at nucleotide position 2570, causing the threonine (T) at amino acid position 857 to be replaced by a lysine (K). 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

0.86

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

.;.;T;T;.;T;.;T;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.88

D;D;D;D;D;.;D;.;D;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.19

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.1

.;.;.;.;.;.;.;L;L;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.9

N;.;N;.;.;N;N;N;.;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;.;D;.;.;D;D;D;.;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;.;.;D;D;D;D;.

Vest4

0.47

MutPred

0.34

.;.;.;.;.;.;.;Gain of methylation at T857 (P = 0.0199);Gain of methylation at T857 (P = 0.0199);.;

MVP

0.38

MPC

1.0

ClinPred

0.55

GERP RS

4.5

Varity_R

0.44

gMVP

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over