3-1356588-T-C

Variant names:

• chr3-1356588-T-C
• rs3772283
• NM_001289080.2:c.1492+4137T>C

Variant summary

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

The NM_001289080.2(CNTN6):​c.1492+4137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 151,900 control chromosomes in the GnomAD database, including 127 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 0.034 (127 hom., cov: 32)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN6	NM_001289080.2	c.1492+4137T>C		intron_variant	Intron 12 of 22	ENST00000446702.7	NP_001276009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN6	ENST00000446702.7	c.1492+4137T>C		intron_variant	Intron 12 of 22	1	NM_001289080.2	ENSP00000407822.2
CNTN6	ENST00000350110.2	c.1492+4137T>C		intron_variant	Intron 12 of 22	1		ENSP00000341882.2
CNTN6	ENST00000397479.6	n.*1630+4137T>C		intron_variant	Intron 11 of 21	2		ENSP00000380616.2

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5241 AN: 151782 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.00930

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.00583

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0456

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

GnomAD4 genome AF: 0.0345 AC: 5239 AN: 151900 Hom.: 127 Cov.: 32 AF XY: 0.0344 AC XY: 2555 AN XY: 74240

African (AFR) AF: 0.00925 AC: 384 AN: 41498

American (AMR) AF: 0.0315 AC: 479 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 185 AN: 3464

East Asian (EAS) AF: 0.00584 AC: 30 AN: 5136

South Asian (SAS) AF: 0.0572 AC: 276 AN: 4828

European-Finnish (FIN) AF: 0.0464 AC: 493 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0482 AC: 3268 AN: 67852

Other (OTH) AF: 0.0451 AC: 95 AN: 2106

Alfa AF: 0.0429 Hom.: 16

Bravo AF: 0.0316

Asia WGS AF: 0.0210 AC: 73 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0090
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs3772283; hg19: chr3-1398272;