12-41016781-CCT-TCG

Variant names:

• chr12-41016781-CCT-TCG
• NM_001843.4:c.2284_2286delCCTinsTCG
• CNTN1 p.Pro762Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001843.4(CNTN1):​c.2284_2286delCCTinsTCG​(p.Pro762Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P762A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTN1 NM_001843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

Genes affected

CNTN1 (HGNC:2171): (contactin 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CNTN1 Gene-Disease associations (from GenCC):

• Compton-North congenital myopathy

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001843.4. 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
	CNTN1	NM_001843.4	MANE Select	c.2284_2286delCCTinsTCG	p.Pro762Ser	missense	N/A	NP_001834.2
	CNTN1	NM_175038.2		c.2251_2253delCCTinsTCG	p.Pro751Ser	missense	N/A	NP_778203.1	Q12860-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.2284_2286delCCTinsTCG	p.Pro762Ser	missense	N/A	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000347616.5	TSL:1	c.2284_2286delCCTinsTCG	p.Pro762Ser	missense	N/A	ENSP00000325660.3	Q12860-1
	CNTN1	ENST00000348761.2	TSL:1	c.2251_2253delCCTinsTCG	p.Pro751Ser	missense	N/A	ENSP00000261160.3	Q12860-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-41410583;