Variant 12-119850217-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5

The NM_001206999.2(CIT):c.473C>G(p.Pro158Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

CIT
NM_001206999.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.64

Variant links:

Genes affected

CIT (HGNC:1985): (citron rho-interacting serine/threonine kinase) This gene encodes a serine/threonine-protein kinase that functions in cell division. Together with the kinesin KIF14, this protein localizes to the central spindle and midbody, and functions to promote efficient cytokinesis. This protein is involved in central nervous system development. Polymorphisms in this gene are associated with bipolar disorder and risk for schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CIT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CIT. . Gene score misZ 3.8214 (greater than the threshold 3.09). Trascript score misZ 5.1629 (greater than threshold 3.09). GenCC has associacion of gene with microcephaly 11, primary, autosomal recessive, microcephaly 17, primary, autosomal recessive, autosomal recessive primary microcephaly.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.806

PP5

Variant 12-119850217-G-C is Pathogenic according to our data. Variant chr12-119850217-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 252994.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIT	NM_001206999.2 linkuse as main transcript	c.473C>G	p.Pro158Arg	missense_variant	5/48	ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7 linkuse as main transcript	c.473C>G	p.Pro158Arg	missense_variant	5/48	1	NM_001206999.2	ENSP00000376306	P1	O14578-4
CIT	ENST00000261833.11 linkuse as main transcript	c.473C>G	p.Pro158Arg	missense_variant	5/47	1		ENSP00000261833		O14578-1
CIT	ENST00000536325.1 linkuse as main transcript	c.224C>G	p.Pro75Arg	missense_variant	2/3	3		ENSP00000443199

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal recessive primary microcephaly

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Sbielas Lab-Department of Human Genetics University of Michigan, University of Michigan Medical School

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T;.;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.0062

MetaRNN

Pathogenic

0.81

D;D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.5

L;L;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.1

N;N;.;N

REVEL

Uncertain

0.43

Sift

Uncertain

0.018

D;D;.;D

Sift4G

Uncertain

0.028

D;D;T;.

Polyphen

0.93

.;P;.;.

Vest4

0.97

MutPred

0.66

Gain of catalytic residue at W156 (P = 0.0016);Gain of catalytic residue at W156 (P = 0.0016);Gain of catalytic residue at W156 (P = 0.0016);.;

MVP

0.83

MPC

0.54

ClinPred

0.91

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.71

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