Variant 3-74285487-C-T 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_020872.3(CNTN3):c.2522G>A(p.Arg841Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,608,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

CNTN3
NM_020872.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.632

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 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=0.009720057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN3	NM_020872.3 linkuse as main transcript	c.2522G>A	p.Arg841Gln	missense_variant	20/23	ENST00000263665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN3	ENST00000263665.7 linkuse as main transcript	c.2522G>A	p.Arg841Gln	missense_variant	20/23	1	NM_020872.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000409

AC:

AN:

151744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.000626

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000530

AC:

129

AN:

243418

Hom.:

AF XY:

0.000607

AC XY:

AN XY:

131706

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00594

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.000539

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000263

Gnomad OTH exome

AF:

0.000682

GnomAD4 exome

AF:

0.000336

AC:

490

AN:

1456614

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

262

AN XY:

724588

show subpopulations

Gnomad4 AFR exome

AF:

0.000332

Gnomad4 AMR exome

AF:

0.000548

Gnomad4 ASJ exome

AF:

0.00593

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.000327

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000178

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000408

AC:

AN:

151862

Hom.:

Cov.:

AF XY:

0.000445

AC XY:

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.000531

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.000626

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000459

Hom.:

Bravo

AF:

0.000468

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.2522G>A (p.R841Q) alteration is located in exon 19 (coding exon 19) of the CNTN3 gene. This alteration results from a G to A substitution at nucleotide position 2522, causing the arginine (R) at amino acid position 841 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 31, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.7

REVEL

Benign

0.12

Sift

Benign

0.29

Sift4G

Benign

0.44

Polyphen

0.018

Vest4

0.25

MVP

0.58

MPC

0.28

ClinPred

0.032

GERP RS

4.4

Varity_R

0.097

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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