Variant 3-1278437-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001289080.2(CNTN6):c.383C>T(p.Thr128Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,608,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CNTN6
NM_001289080.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.04

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010070175).

BP6

Variant 3-1278437-C-T is Benign according to our data. Variant chr3-1278437-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044328.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN6	NM_001289080.2 linkuse as main transcript	c.383C>T	p.Thr128Ile	missense_variant	5/23	ENST00000446702.7	NP_001276009.1	Q9UQ52A1LMA8B4DGV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN6	ENST00000446702.7 linkuse as main transcript	c.383C>T	p.Thr128Ile	missense_variant	5/23	1	NM_001289080.2	ENSP00000407822.2		Q9UQ52

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

185

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000289

AC:

AN:

249480

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

134772

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000105

AC:

153

AN:

1455984

Hom.:

Cov.:

AF XY:

0.0000857

AC XY:

AN XY:

723692

show subpopulations

Gnomad4 AFR exome

AF:

0.00405

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.00122

AC:

185

AN:

152176

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00429

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000177

Hom.:

Bravo

AF:

0.00135

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000346

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CNTN6-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 04, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.62

.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.053

Sift

Benign

0.11

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.32

B;B

Vest4

0.20

MVP

0.79

MPC

0.0070

ClinPred

0.047

GERP RS

4.1

Varity_R

0.17

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over