NM_001843.4:c.49A>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001843.4(CNTN1):c.49A>C(p.Thr17Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CNTN1
NM_001843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00800

Publications

0 publications found

Variant links:

Genes affected

CNTN1 (HGNC:2171): (contactin 1) 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. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CNTN1 Gene-Disease associations (from GenCC):

Compton-North congenital myopathy
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

CNTN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19369236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4 link	c.49A>C	p.Thr17Pro	missense_variant	Exon 2 of 24	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7 link	c.49A>C	p.Thr17Pro	missense_variant	Exon 2 of 24	1	NM_001843.4	ENSP00000447006.1		Q12860-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250402

AF XY:

0.00000739

show subpopulations

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455024

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33312

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39568

South Asian (SAS)

AF:

0.00

AC:

AN:

86036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106680

Other (OTH)

AF:

0.00

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Compton-North congenital myopathy

Uncertain:1

Oct 03, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 17 of the CNTN1 protein (p.Thr17Pro). This variant is present in population databases (rs773695120, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CNTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2044129). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CNTN1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Uncertain

0.61

.;.;D;T;T;.;T;D;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.54

.;T;.;T;T;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.19

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N;.;.;N;.;N;N

PhyloP100

-0.0080

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.0

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.087

Sift

Benign

0.21

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.23

T;D;T;D;D;T;D;T;T

Polyphen

0.10

B;.;B;.;.;B;.;B;B

Vest4

0.34

MutPred

0.56

Loss of glycosylation at T17 (P = 0.0549);Loss of glycosylation at T17 (P = 0.0549);Loss of glycosylation at T17 (P = 0.0549);Loss of glycosylation at T17 (P = 0.0549);Loss of glycosylation at T17 (P = 0.0549);Loss of glycosylation at T17 (P = 0.0549);Loss of glycosylation at T17 (P = 0.0549);Loss of glycosylation at T17 (P = 0.0549);Loss of glycosylation at T17 (P = 0.0549);

MVP

0.83

MPC

0.39

ClinPred

0.035

GERP RS

-5.9

PromoterAI

0.012

Neutral

(source)

Varity_R

0.14

gMVP

0.78

Mutation Taster

=90/10

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over