12-119690286-G-A

Variant names:

• chr12-119690286-G-A
• rs766445204
• NM_001206999.2:c.6051C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001206999.2(CIT):​c.6051C>T​(p.Pro2017Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,584,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: CIT NM_001206999.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.646
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly 17, primary, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.086).
• BP6: Variant 12-119690286-G-A is Benign according to our data. Variant chr12-119690286-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 732552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.646 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIT	NM_001206999.2	c.6051C>T	p.Pro2017Pro	synonymous_variant	Exon 47 of 48	ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.6051C>T	p.Pro2017Pro	synonymous_variant	Exon 47 of 48	1	NM_001206999.2	ENSP00000376306.2

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152188 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000190 AC: 41 AN: 215754 AF XY: 0.000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000206

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000326

Gnomad OTH exome AF: 0.000378

GnomAD4 exome AF: 0.000248 AC: 355 AN: 1432644 Hom.: 0 Cov.: 31 AF XY: 0.000255 AC XY: 182 AN XY: 713172

African (AFR) AF: 0.0000929 AC: 3 AN: 32294

American (AMR) AF: 0.000273 AC: 11 AN: 40232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25398

East Asian (EAS) AF: 0.00 AC: 0 AN: 38932

South Asian (SAS) AF: 0.00 AC: 0 AN: 84404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.000302 AC: 334 AN: 1106028

Other (OTH) AF: 0.000118 AC: 7 AN: 59494

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152188 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74338

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000205 Hom.: 0

Bravo AF: 0.000174

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CIT: BP4, BP7 -

Nov 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.1
DANN	Benign	0.85
PhyloP100		-0.65
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs766445204; hg19: chr12-120128091;