NM_001289080.2:c.288C>T

Variant names:

• chr3-1227923-C-T
• rs61739199
• NM_001289080.2:c.288C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001289080.2(CNTN6):​c.288C>T​(p.Gly96Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0093 in 1,613,952 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0096 (102 hom.)
• Consequence: CNTN6 NM_001289080.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.764
• 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 -16 ACMG points.

• BP6: Variant 3-1227923-C-T is Benign according to our data. Variant chr3-1227923-C-T is described in ClinVar as Benign. ClinVar VariationId is 773864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00599 (912/152208) while in subpopulation SAS AF = 0.0186 (90/4826). AF 95% confidence interval is 0.0155. There are 10 homozygotes in GnomAd4. There are 400 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 912 AD,Unknown gene.

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.288C>T	p.Gly96Gly	synonymous	Exon 4 of 23	NP_001276009.1	Q9UQ52
	CNTN6	NM_001349350.2		c.288C>T	p.Gly96Gly	synonymous	Exon 6 of 25	NP_001336279.1	Q9UQ52
	CNTN6	NM_001349351.2		c.288C>T	p.Gly96Gly	synonymous	Exon 6 of 25	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.288C>T	p.Gly96Gly	synonymous	Exon 4 of 23	ENSP00000407822.2	Q9UQ52
	CNTN6	ENST00000350110.2	TSL:1	c.288C>T	p.Gly96Gly	synonymous	Exon 4 of 23	ENSP00000341882.2	Q9UQ52
	CNTN6	ENST00000394261.2	TSL:1	n.*266C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000377804.2	F8WDQ0

Frequencies

GnomAD3 genomes AF: 0.00600 AC: 912 AN: 152090 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00970

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00756 AC: 1899 AN: 251276 AF XY: 0.00852

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00257

Gnomad ASJ exome AF: 0.00625

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00397

Gnomad NFE exome AF: 0.00920

Gnomad OTH exome AF: 0.00881

GnomAD4 exome AF: 0.00964 AC: 14092 AN: 1461744 Hom.: 102 Cov.: 32 AF XY: 0.00984 AC XY: 7155 AN XY: 727152

African (AFR) AF: 0.000986 AC: 33 AN: 33478

American (AMR) AF: 0.00277 AC: 124 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00559 AC: 146 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.0172 AC: 1485 AN: 86244

European-Finnish (FIN) AF: 0.00470 AC: 251 AN: 53418

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5768

European-Non Finnish (NFE) AF: 0.0104 AC: 11517 AN: 1111904

Other (OTH) AF: 0.00841 AC: 508 AN: 60392

GnomAD4 genome AF: 0.00599 AC: 912 AN: 152208 Hom.: 10 Cov.: 32 AF XY: 0.00538 AC XY: 400 AN XY: 74414

African (AFR) AF: 0.00113 AC: 47 AN: 41544

American (AMR) AF: 0.00183 AC: 28 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.0186 AC: 90 AN: 4826

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10588

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00970 AC: 660 AN: 68008

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00863 Hom.: 5

Bravo AF: 0.00543

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.0101

EpiControl AF: 0.00788

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CNTN6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.44
PhyloP100		0.76
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.44		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61739199; hg19: chr3-1269607;