rs45588035

chr9-128180748-C-Achr9-128180748-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001131016.2(CIZ1):c.655G>T(p.Ala219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,608,700 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A219T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000072 (1 hom.)
• Consequence: CIZ1 NM_001131016.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007142484).
• BP6: Variant 9-128180748-C-A is Benign according to our data. Variant chr9-128180748-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 698000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIZ1	NM_001131016.2	c.655G>T	p.Ala219Ser	missense_variant	6/17	ENST00000372938.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIZ1	ENST00000372938.10	c.655G>T	p.Ala219Ser	missense_variant	6/17	1	NM_001131016.2	P2

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000130 AC: 32 AN: 245764 Hom.: 0 AF XY: 0.0000973 AC XY: 13 AN XY: 133670

Gnomad AFR exome AF: 0.00147

Gnomad AMR exome AF: 0.000185

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000721 AC: 105 AN: 1456452 Hom.: 1 Cov.: 30 AF XY: 0.0000607 AC XY: 44 AN XY: 725072

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.000210

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000581

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.000332

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74442

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00000869 Hom.: 41

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dystonic disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.16
Dann	Benign	0.68
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.60	T;T;T;T;T;.;T;.;T;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.0071	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.22	N;.;N;.;.;N;N;N;.;N;N
REVEL	Benign	0.022
Sift	Benign	0.14	T;.;T;.;.;T;T;T;.;T;T
Sift4G	Benign	0.48	T;T;T;T;T;T;T;T;T;T;.
Polyphen		0.39	B;.;B;.;.;B;B;B;B;.;.
Vest4		0.11
MutPred		0.20		.;.;Gain of phosphorylation at A219 (P = 7e-04);.;.;Gain of phosphorylation at A219 (P = 7e-04);Gain of phosphorylation at A219 (P = 7e-04);Gain of phosphorylation at A219 (P = 7e-04);Gain of phosphorylation at A219 (P = 7e-04);.;Gain of phosphorylation at A219 (P = 7e-04);
MVP		0.58
MPC		0.27
ClinPred		0.0036	T
GERP RS		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.023

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

Other links and lift over

dbSNP: rs45588035; hg19: chr9-130943027;