dbSNP rs147055375: CNTN3:p.Val1019Ile (chr3-74264433-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_020872.3(CNTN3):c.3055G>A(p.Val1019Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000629 in 1,609,820 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 5 hom. )

Consequence

CNTN3
NM_020872.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.368

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033460557).

BP6

Variant 3-74264433-C-T is Benign according to our data. Variant chr3-74264433-C-T is described in ClinVar as Benign. ClinVar VariationId is 3045546.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020872.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN3	NM_020872.3	MANE Select	c.3055G>A	p.Val1019Ile	missense	Exon 23 of 23	NP_065923.1	Q9P232
	CNTN3	NM_001393376.1		c.3055G>A	p.Val1019Ile	missense	Exon 23 of 23	NP_001380305.1	Q9P232

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNTN3	ENST00000263665.7	TSL:1 MANE Select	c.3055G>A	p.Val1019Ile	missense	Exon 23 of 23	ENSP00000263665.6	Q9P232
CNTN3	ENST00000962150.1		c.3049G>A	p.Val1017Ile	missense	Exon 24 of 24	ENSP00000632209.1
CNTN3	ENST00000962149.1		c.2740G>A	p.Val914Ile	missense	Exon 21 of 21	ENSP00000632208.1

Frequencies

GnomAD3 genomes

AF:

0.000921

AC:

140

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00128

AC:

321

AN:

249826

AF XY:

0.00123

show subpopulations

Gnomad AFR exome

AF:

0.000926

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.000597

AC:

870

AN:

1457734

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

426

AN XY:

725358

show subpopulations

African (AFR)

AF:

0.000810

AC:

AN:

33328

American (AMR)

AF:

0.000292

AC:

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.0232

AC:

603

AN:

26042

East Asian (EAS)

AF:

0.00

AC:

AN:

39594

South Asian (SAS)

AF:

0.00

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000103

AC:

114

AN:

1108752

Other (OTH)

AF:

0.00184

AC:

111

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

121

162

202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000934

AC:

142

AN:

152086

Hom.:

Cov.:

AF XY:

0.000982

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.000939

AC:

AN:

41514

American (AMR)

AF:

0.000263

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67956

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00113

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000947

AC:

115

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000165

EpiControl

AF:

0.000419

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CNTN3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.8

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.046

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.53

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

PhyloP100

-0.37

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.060

REVEL

Benign

0.092

Sift

Benign

0.22

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.083

MVP

0.45

MPC

0.19

ClinPred

0.0017

GERP RS

2.0

Varity_R

0.035

gMVP

0.37

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over