rs369660377

Variant names:

• chr9-128166300-C-A
• NM_001131016.2:c.2594G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-128166300-C-A
• chr9-128166300-C-G
• chr9-128166300-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

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 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
CIZ1	NM_001131016.2	c.2594G>T	p.Arg865Leu	missense_variant	Exon 17 of 17	ENST00000372938.10	NP_001124488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000372938.10	c.2594G>T	p.Arg865Leu	missense_variant	Exon 17 of 17	1	NM_001131016.2	ENSP00000362029.5

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

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;