dbSNP rs200776867: CNTN6:p.Ile47Val (chr3-1220770-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001289080.2(CNTN6):c.139A>G(p.Ile47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I47F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CNTN6
NM_001289080.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.425

Publications

1 publications found

Variant links:

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

CNTN6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030118197).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTN6	NM_001289080.2	MANE Select	c.139A>G	p.Ile47Val	missense	Exon 3 of 23	NP_001276009.1	Q9UQ52
CNTN6	NM_001349350.2		c.139A>G	p.Ile47Val	missense	Exon 5 of 25	NP_001336279.1	Q9UQ52
CNTN6	NM_001349351.2		c.139A>G	p.Ile47Val	missense	Exon 5 of 25	NP_001336280.1	Q9UQ52

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTN6	ENST00000446702.7	TSL:1 MANE Select	c.139A>G	p.Ile47Val	missense	Exon 3 of 23	ENSP00000407822.2	Q9UQ52
CNTN6	ENST00000350110.2	TSL:1	c.139A>G	p.Ile47Val	missense	Exon 3 of 23	ENSP00000341882.2	Q9UQ52
CNTN6	ENST00000394261.2	TSL:1	n.*117A>G		non_coding_transcript_exon	Exon 4 of 8	ENSP00000377804.2	F8WDQ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

250864

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.058

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.38

M_CAP

Benign

0.0041

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.17

PhyloP100

0.42

PrimateAI

Benign

0.29

PROVEAN

Benign

0.29

REVEL

Benign

0.048

Sift

Benign

0.56

Sift4G

Benign

1.0

Polyphen

0.016

Vest4

0.062

MutPred

0.37

Loss of ubiquitination at K43 (P = 0.1016)

MVP

0.18

MPC

0.0065

ClinPred

0.037

GERP RS

3.4

Varity_R

0.025

gMVP

0.17

Mutation Taster

=251/49

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over