rs10510207

Variant names:

• chr3-1292846-G-T
• rs10510207
• NM_001289080.2:c.455-2755G>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.455-2755G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,034 control chromosomes in the GnomAD database, including 813 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 0.097 (813 hom., cov: 32)
• Consequence: CNTN6 NM_001289080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	NM_001289080.2	MANE Select	c.455-2755G>T		intron	N/A	NP_001276009.1	Q9UQ52
	CNTN6	NM_001349350.2		c.455-2755G>T		intron	N/A	NP_001336279.1	Q9UQ52
	CNTN6	NM_001349351.2		c.455-2755G>T		intron	N/A	NP_001336280.1	Q9UQ52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN6	ENST00000446702.7	TSL:1 MANE Select	c.455-2755G>T		intron	N/A	ENSP00000407822.2	Q9UQ52
	CNTN6	ENST00000350110.2	TSL:1	c.455-2755G>T		intron	N/A	ENSP00000341882.2	Q9UQ52
	CNTN6	ENST00000394261.2	TSL:1	n.*433-2755G>T		intron	N/A	ENSP00000377804.2	F8WDQ0

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14789 AN: 151914 Hom.: 812 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0974 AC: 14812 AN: 152034 Hom.: 813 Cov.: 32 AF XY: 0.0950 AC XY: 7059 AN XY: 74334

African (AFR) AF: 0.154 AC: 6369 AN: 41442

American (AMR) AF: 0.0629 AC: 960 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 281 AN: 3468

East Asian (EAS) AF: 0.123 AC: 637 AN: 5174

South Asian (SAS) AF: 0.0391 AC: 188 AN: 4812

European-Finnish (FIN) AF: 0.0556 AC: 589 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0807 AC: 5483 AN: 67960

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0821 Hom.: 925

Bravo AF: 0.102

Asia WGS AF: 0.0860 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.60
PhyloP100		1.3
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: rs10510207; hg19: chr3-1334530;