Variant 3-74285307-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000263665.7(CNTN3):c.2702C>T(p.Thr901Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0096 in 1,601,278 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0098 ( 81 hom. )

Consequence

CNTN3
ENST00000263665.7 missense, splice_region

Scores

Splicing: ADA: 0.01614

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.83

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004834354).

BP6

Variant 3-74285307-G-A is Benign according to our data. Variant chr3-74285307-G-A is described in ClinVar as [Benign]. Clinvar id is 774423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN3	NM_020872.3 linkuse as main transcript	c.2702C>T	p.Thr901Met	missense_variant, splice_region_variant	20/23	ENST00000263665.7	NP_065923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN3	ENST00000263665.7 linkuse as main transcript	c.2702C>T	p.Thr901Met	missense_variant, splice_region_variant	20/23	1	NM_020872.3	ENSP00000263665	P1

Frequencies

GnomAD3 genomes

AF:

0.00806

AC:

1225

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.00531

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00823

AC:

1956

AN:

237704

Hom.:

AF XY:

0.00820

AC XY:

1060

AN XY:

129228

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.00132

Gnomad EAS exome

AF:

0.000117

Gnomad SAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.00835

GnomAD4 exome

AF:

0.00976

AC:

14150

AN:

1449174

Hom.:

Cov.:

AF XY:

0.00955

AC XY:

6888

AN XY:

721480

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00299

Gnomad4 ASJ exome

AF:

0.00170

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00302

Gnomad4 FIN exome

AF:

0.0131

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00852

GnomAD4 genome

AF:

0.00805

AC:

1224

AN:

152104

Hom.:

Cov.:

AF XY:

0.00792

AC XY:

589

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00531

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.0138

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00717

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.00928

AC:

1126

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.46

MutationTaster

Benign

0.74

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.4

REVEL

Benign

0.090

Sift

Benign

0.034

Sift4G

Benign

0.090

Polyphen

0.0040

Vest4

0.21

MVP

0.49

MPC

0.25

ClinPred

0.018

GERP RS

2.1

Varity_R

0.030

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.016

dbscSNV1_RF

Benign

0.18

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