Variant 3-74295205-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_020872.3(CNTN3):c.2433A>C(p.Ala811=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,610,212 control chromosomes in the GnomAD database, including 18,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1249 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17664 hom. )

Consequence

CNTN3
NM_020872.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.475

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-74295205-T-G is Benign according to our data. Variant chr3-74295205-T-G is described in ClinVar as [Benign]. Clinvar id is 3055362.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.475 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 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.2433A>C	p.Ala811=	synonymous_variant	19/23	ENST00000263665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN3	ENST00000263665.7 linkuse as main transcript	c.2433A>C	p.Ala811=	synonymous_variant	19/23	1	NM_020872.3	P1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16941

AN:

152170

Hom.:

1251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.0888

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.0289

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.128

AC:

32187

AN:

250704

Hom.:

2485

AF XY:

0.135

AC XY:

18254

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.0694

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.0305

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.150

AC:

219182

AN:

1457924

Hom.:

17664

Cov.:

AF XY:

0.152

AC XY:

110228

AN XY:

725398

show subpopulations

Gnomad4 AFR exome

AF:

0.0233

Gnomad4 AMR exome

AF:

0.0729

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.0271

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.160

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.111

AC:

16941

AN:

152288

Hom.:

1249

Cov.:

AF XY:

0.110

AC XY:

8204

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.0886

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.0293

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.149

Hom.:

4529

Bravo

AF:

0.102

Asia WGS

AF:

0.117

AC:

407

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

Oct 30, 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

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.2

DANN

Benign

0.53

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