3-1303741-C-T

Variant names:

• chr3-1303741-C-T
• rs9861887
• NM_001289080.2:c.761+5750C>T

Variant summary

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

The NM_001289080.2(CNTN6):​c.761+5750C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,904 control chromosomes in the GnomAD database, including 36,319 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 0.67 (36319 hom., cov: 31)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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.761+5750C>T		intron	N/A	NP_001276009.1
	CNTN6	NM_001349350.2		c.761+5750C>T		intron	N/A	NP_001336279.1
	CNTN6	NM_001349351.2		c.761+5750C>T		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.761+5750C>T		intron	N/A	ENSP00000407822.2
	CNTN6	ENST00000350110.2	TSL:1	c.761+5750C>T		intron	N/A	ENSP00000341882.2
	CNTN6	ENST00000397479.6	TSL:2	n.*899+5750C>T		intron	N/A	ENSP00000380616.2

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101658 AN: 151786 Hom.: 36323 Cov.: 31

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.669 AC: 101682 AN: 151904 Hom.: 36319 Cov.: 31 AF XY: 0.674 AC XY: 50019 AN XY: 74246

African (AFR) AF: 0.402 AC: 16622 AN: 41364

American (AMR) AF: 0.773 AC: 11811 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2528 AN: 3466

East Asian (EAS) AF: 0.997 AC: 5150 AN: 5166

South Asian (SAS) AF: 0.867 AC: 4179 AN: 4822

European-Finnish (FIN) AF: 0.708 AC: 7451 AN: 10524

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.760 AC: 51671 AN: 67976

Other (OTH) AF: 0.688 AC: 1451 AN: 2108

Alfa AF: 0.702 Hom.: 8950

Bravo AF: 0.662

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.084
DANN	Benign	0.41
PhyloP100		-1.8
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: rs9861887; hg19: chr3-1345425;