3-1220687-G-T

Variant names:

• chr3-1220687-G-T
• rs1292255697
• NM_001289080.2:c.56G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001289081.2(CNTN6):​c.-161G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTN6 NM_001289081.2 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.8722
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919
• Publications: 0 publications found

Genes affected

CNTN6 (HGNC:2176): (contactin 6) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

CNTN6 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289081.2. 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
	CNTN6	NM_001289080.2	MANE Select	c.56G>T	p.Gly19Val	missense splice_region	Exon 3 of 23	NP_001276009.1	Q9UQ52
	CNTN6	NM_001289081.2		c.-161G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 22	NP_001276010.1
	CNTN6	NM_001349359.2		c.-882G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 21	NP_001336288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	ENST00000446702.7	TSL:1 MANE Select	c.56G>T	p.Gly19Val	missense splice_region	Exon 3 of 23	ENSP00000407822.2	Q9UQ52
	CNTN6	ENST00000350110.2	TSL:1	c.56G>T	p.Gly19Val	missense splice_region	Exon 3 of 23	ENSP00000341882.2	Q9UQ52
	CNTN6	ENST00000394261.2	TSL:1	n.*34G>T		splice_region non_coding_transcript_exon	Exon 4 of 8	ENSP00000377804.2	F8WDQ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.92
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.017	D
Polyphen		0.95	P
Vest4		0.44
MutPred		0.53		Loss of helix (P = 0.0196)
MVP		0.85
MPC		0.0052
ClinPred		0.80	D
GERP RS		4.8
Varity_R		0.19
gMVP		0.28
Mutation Taster		=272/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.87
dbscSNV1_RF	Benign	0.47
SpliceAI score (max)		0.75		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.75		Position offset: 0

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

Other links and lift over

dbSNP: rs1292255697; hg19: chr3-1262371; COSMIC: COSV100610332;