12-119690229-G-C

Variant names:

• chr12-119690229-G-C
• NM_001206999.2:c.6108C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001206999.2(CIT):​c.6108C>G​(p.Pro2036Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CIT NM_001206999.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.46
• 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.072).
• BP6: Variant 12-119690229-G-C is Benign according to our data. Variant chr12-119690229-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3342096.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.46 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	NM_001206999.2	MANE Select	c.6108C>G	p.Pro2036Pro	synonymous	Exon 47 of 48	NP_001193928.1	O14578-4
	CIT	NM_007174.3		c.5982C>G	p.Pro1994Pro	synonymous	Exon 46 of 47	NP_009105.1	O14578-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	ENST00000392521.7	TSL:1 MANE Select	c.6108C>G	p.Pro2036Pro	synonymous	Exon 47 of 48	ENSP00000376306.2	O14578-4
	CIT	ENST00000261833.11	TSL:1	c.5982C>G	p.Pro1994Pro	synonymous	Exon 46 of 47	ENSP00000261833.7	O14578-1
	CIT	ENST00000928243.1		c.6105C>G	p.Pro2035Pro	synonymous	Exon 47 of 48	ENSP00000598302.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1383134 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 684558

African (AFR) AF: 0.00 AC: 0 AN: 29312

American (AMR) AF: 0.00 AC: 0 AN: 30342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23130

East Asian (EAS) AF: 0.00 AC: 0 AN: 36704

South Asian (SAS) AF: 0.00 AC: 0 AN: 76102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5486

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084090

Other (OTH) AF: 0.00 AC: 0 AN: 57330

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.032
DANN	Benign	0.69
PhyloP100		-4.5

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

hg19: chr12-120128034;