Variant 3-1220761-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001289080.2(CNTN6):c.130T>C(p.Ser44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,613,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

CNTN6
NM_001289080.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.779

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03044635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN6	NM_001289080.2 linkuse as main transcript	c.130T>C	p.Ser44Pro	missense_variant	3/23	ENST00000446702.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CNTN6	ENST00000446702.7 linkuse as main transcript	c.130T>C	p.Ser44Pro	missense_variant	3/23	1	NM_001289080.2	P1
CNTN6	ENST00000350110.2 linkuse as main transcript	c.130T>C	p.Ser44Pro	missense_variant	3/23	1		P1
CNTN6	ENST00000394261.2 linkuse as main transcript	c.*108T>C		3_prime_UTR_variant, NMD_transcript_variant	4/8	1
CNTN6	ENST00000397479.6 linkuse as main transcript	c.*268T>C		3_prime_UTR_variant, NMD_transcript_variant	2/22	2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000183

AC:

AN:

250942

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00119

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:

0.0000264

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1460762

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2023

The c.130T>C (p.S44P) alteration is located in exon 3 (coding exon 2) of the CNTN6 gene. This alteration results from a T to C substitution at nucleotide position 130, causing the serine (S) at amino acid position 44 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.091

M_CAP

Benign

0.0041

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

0.54

D;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.069

Sift

Benign

0.14

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0050

B;B

Vest4

0.11

MVP

0.72

MPC

0.0043

ClinPred

0.031

GERP RS

5.8

Varity_R

0.21

gMVP

0.58

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