3-1259446-C-A

Variant names:

• chr3-1259446-C-A
• rs9815195
• NM_001289080.2:c.359-18967C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001289080.2(CNTN6):​c.359-18967C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,840 control chromosomes in the GnomAD database, including 7,937 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7937 hom., cov: 33)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289080.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	NM_001289080.2	MANE Select	c.359-18967C>A		intron	N/A	NP_001276009.1
	CNTN6	NM_001349350.2		c.359-18967C>A		intron	N/A	NP_001336279.1
	CNTN6	NM_001349351.2		c.359-18967C>A		intron	N/A	NP_001336280.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	ENST00000446702.7	TSL:1 MANE Select	c.359-18967C>A		intron	N/A	ENSP00000407822.2
	CNTN6	ENST00000350110.2	TSL:1	c.359-18967C>A		intron	N/A	ENSP00000341882.2
	CNTN6	ENST00000394261.2	TSL:1	n.*337-18967C>A		intron	N/A	ENSP00000377804.2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43985 AN: 151722 Hom.: 7900 Cov.: 33

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.290 AC: 44072 AN: 151840 Hom.: 7937 Cov.: 33 AF XY: 0.286 AC XY: 21192 AN XY: 74218

African (AFR) AF: 0.511 AC: 21195 AN: 41440

American (AMR) AF: 0.250 AC: 3807 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3468

East Asian (EAS) AF: 0.141 AC: 730 AN: 5168

South Asian (SAS) AF: 0.171 AC: 824 AN: 4806

European-Finnish (FIN) AF: 0.185 AC: 1948 AN: 10504

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13878 AN: 67926

Other (OTH) AF: 0.254 AC: 534 AN: 2102

Alfa AF: 0.233 Hom.: 2883

Bravo AF: 0.307

Asia WGS AF: 0.193 AC: 672 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.44
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs9815195; hg19: chr3-1301130; COSMIC: COSV63174444;