Variant 3-74299911-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020872.3(CNTN3):c.2123A>G(p.Asn708Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 1,603,772 control chromosomes in the GnomAD database, including 4,930 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.081 ( 615 hom., cov: 32)

Exomes 𝑓: 0.067 ( 4315 hom. )

Consequence

CNTN3
NM_020872.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.58

Variant links:

Genes affected

CNTN3 (HGNC:2173): (contactin 3) Predicted to be involved in cell adhesion and nervous system development. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

CNTN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014759898).

BP6

Variant 3-74299911-T-C is Benign according to our data. Variant chr3-74299911-T-C is described in ClinVar as [Benign]. Clinvar id is 3056967.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN3	NM_020872.3 linkuse as main transcript	c.2123A>G	p.Asn708Ser	missense_variant	17/23	ENST00000263665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN3	ENST00000263665.7 linkuse as main transcript	c.2123A>G	p.Asn708Ser	missense_variant	17/23	1	NM_020872.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0808

AC:

12291

AN:

152038

Hom.:

614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0857

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0580

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0569

Gnomad OTH

AF:

0.0907

GnomAD3 exomes

AF:

0.0841

AC:

20576

AN:

244768

Hom.:

1199

AF XY:

0.0839

AC XY:

11094

AN XY:

132298

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0932

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0550

Gnomad NFE exome

AF:

0.0569

Gnomad OTH exome

AF:

0.0824

GnomAD4 exome

AF:

0.0675

AC:

97981

AN:

1451616

Hom.:

4315

Cov.:

AF XY:

0.0684

AC XY:

49341

AN XY:

721664

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.0915

Gnomad4 ASJ exome

AF:

0.0480

Gnomad4 EAS exome

AF:

0.234

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0554

Gnomad4 NFE exome

AF:

0.0567

Gnomad4 OTH exome

AF:

0.0779

GnomAD4 genome

AF:

0.0809

AC:

12307

AN:

152156

Hom.:

615

Cov.:

AF XY:

0.0824

AC XY:

6132

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0857

Gnomad4 ASJ

AF:

0.0565

Gnomad4 EAS

AF:

0.229

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.0580

Gnomad4 NFE

AF:

0.0569

Gnomad4 OTH

AF:

0.0974

Alfa

AF:

0.0695

Hom.:

1030

Bravo

AF:

0.0856

TwinsUK

AF:

0.0531

AC:

197

ALSPAC

AF:

0.0615

AC:

237

ESP6500AA

AF:

0.106

AC:

465

ESP6500EA

AF:

0.0550

AC:

473

ExAC

AF:

0.0856

AC:

10392

Asia WGS

AF:

0.194

AC:

674

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CNTN3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 2019

This variant is classified as 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

Benign

0.10

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.020

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.2

MutationTaster

Benign

0.99

PrimateAI

Benign

0.37

PROVEAN

Benign

0.61

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.015

MPC

0.19

ClinPred

0.00097

GERP RS

2.7

Varity_R

0.055

gMVP

0.29

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