3-1268727-C-T

Variant names:

• chr3-1268727-C-T
• rs9835344
• NM_001289080.2:c.359-9686C>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.359-9686C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,742 control chromosomes in the GnomAD database, including 23,142 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 0.54 (23142 hom., cov: 31)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN6	NM_001289080.2	c.359-9686C>T		intron_variant	Intron 4 of 22	ENST00000446702.7	NP_001276009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN6	ENST00000446702.7	c.359-9686C>T		intron_variant	Intron 4 of 22	1	NM_001289080.2	ENSP00000407822.2
CNTN6	ENST00000350110.2	c.359-9686C>T		intron_variant	Intron 4 of 22	1		ENSP00000341882.2
CNTN6	ENST00000394261.2	n.*337-9686C>T		intron_variant	Intron 5 of 7	1		ENSP00000377804.2
CNTN6	ENST00000397479.6	n.*497-9686C>T		intron_variant	Intron 3 of 21	2		ENSP00000380616.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81642 AN: 151626 Hom.: 23092 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.539 AC: 81746 AN: 151742 Hom.: 23142 Cov.: 31 AF XY: 0.546 AC XY: 40515 AN XY: 74150

African (AFR) AF: 0.654 AC: 27034 AN: 41338

American (AMR) AF: 0.622 AC: 9494 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3468

East Asian (EAS) AF: 0.823 AC: 4239 AN: 5150

South Asian (SAS) AF: 0.704 AC: 3385 AN: 4810

European-Finnish (FIN) AF: 0.489 AC: 5128 AN: 10488

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29226 AN: 67930

Other (OTH) AF: 0.525 AC: 1107 AN: 2108

Alfa AF: 0.485 Hom.: 4214

Bravo AF: 0.552

Asia WGS AF: 0.755 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.7
DANN	Benign	0.53
PhyloP100		0.98
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: rs9835344; hg19: chr3-1310411;