rs543683676

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_020872.3(CNTN3):​c.2167-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,559,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

CNTN3
NM_020872.3 splice_region, intron

Scores

2
Splicing: ADA: 0.06047
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.59

Publications

0 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 3-74298196-A-G is Benign according to our data. Variant chr3-74298196-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 745414.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNTN3NM_020872.3 linkc.2167-5T>C splice_region_variant, intron_variant Intron 17 of 22 ENST00000263665.7 NP_065923.1 Q9P232

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNTN3ENST00000263665.7 linkc.2167-5T>C splice_region_variant, intron_variant Intron 17 of 22 1 NM_020872.3 ENSP00000263665.6 Q9P232

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000235
AC:
5
AN:
212658
AF XY:
0.00000884
show subpopulations
Gnomad AFR exome
AF:
0.000315
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000853
AC:
12
AN:
1407164
Hom.:
0
Cov.:
28
AF XY:
0.00000864
AC XY:
6
AN XY:
694838
show subpopulations
African (AFR)
AF:
0.000374
AC:
12
AN:
32118
American (AMR)
AF:
0.00
AC:
0
AN:
39414
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22724
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39074
South Asian (SAS)
AF:
0.00
AC:
0
AN:
77496
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51558
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5486
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1081270
Other (OTH)
AF:
0.00
AC:
0
AN:
58024
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.471
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000460
AC:
7
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74462
show subpopulations
African (AFR)
AF:
0.000168
AC:
7
AN:
41562
American (AMR)
AF:
0.00
AC:
0
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5160
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68024
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000986
Hom.:
0
Bravo
AF:
0.0000453

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 15, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
12
DANN
Benign
0.73
PhyloP100
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.060
dbscSNV1_RF
Benign
0.096
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs543683676; hg19: chr3-74347347; API