Genetic Variant CNTN1:p.Thr17Ala (chr12-40908481-A-G) – ACMG Classification: Uncertain_significance (0 pts)

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>G(p.Thr17Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T17P) has been classified 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

Not reported in ClinVar

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:

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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=0.099877656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4 link	c.49A>G	p.Thr17Ala	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>G	p.Thr17Ala	missense_variant	Exon 2 of 24	1	NM_001843.4	ENSP00000447006.1		Q12860-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455024

Hom.:

Cov.:

AF XY:

0.00

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: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.7

(source)

DANN

Benign

0.22

DEOGEN2

Uncertain

0.45

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.56

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

M_CAP

Benign

0.017

MetaRNN

Benign

0.10

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

0.32

PROVEAN

Benign

-0.020

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

REVEL

Benign

0.055

Sift

Benign

0.52

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

Sift4G

Benign

0.57

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

Polyphen

0.0020

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

Vest4

0.089

MutPred

0.45

Loss of glycosylation at T17 (P = 0.0421);Loss of glycosylation at T17 (P = 0.0421);Loss of glycosylation at T17 (P = 0.0421);Loss of glycosylation at T17 (P = 0.0421);Loss of glycosylation at T17 (P = 0.0421);Loss of glycosylation at T17 (P = 0.0421);Loss of glycosylation at T17 (P = 0.0421);Loss of glycosylation at T17 (P = 0.0421);Loss of glycosylation at T17 (P = 0.0421);

MVP

0.46

MPC

0.30

ClinPred

0.020

GERP RS

-5.9

PromoterAI

0.019

Neutral

(source)

Varity_R

0.028

gMVP

0.70

Mutation Taster

=93/7

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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12-40908481-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over