3-74299911-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_020872.3(CNTN3):ā€‹c.2123A>Gā€‹(p.Asn708Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 1,603,772 control chromosomes in the GnomAD database, including 4,930 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.081 ( 615 hom., cov: 32)
Exomes š‘“: 0.067 ( 4315 hom. )

Consequence

CNTN3
NM_020872.3 missense

Scores

1
17

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.58
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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0014759898).
BP6
Variant 3-74299911-T-C is Benign according to our data. Variant chr3-74299911-T-C is described in ClinVar as [Benign]. Clinvar id is 3056967.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNTN3NM_020872.3 linkuse as main transcriptc.2123A>G p.Asn708Ser missense_variant 17/23 ENST00000263665.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNTN3ENST00000263665.7 linkuse as main transcriptc.2123A>G p.Asn708Ser missense_variant 17/231 NM_020872.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0808
AC:
12291
AN:
152038
Hom.:
614
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.106
Gnomad AMI
AF:
0.0307
Gnomad AMR
AF:
0.0857
Gnomad ASJ
AF:
0.0565
Gnomad EAS
AF:
0.230
Gnomad SAS
AF:
0.102
Gnomad FIN
AF:
0.0580
Gnomad MID
AF:
0.0981
Gnomad NFE
AF:
0.0569
Gnomad OTH
AF:
0.0907
GnomAD3 exomes
AF:
0.0841
AC:
20576
AN:
244768
Hom.:
1199
AF XY:
0.0839
AC XY:
11094
AN XY:
132298
show subpopulations
Gnomad AFR exome
AF:
0.105
Gnomad AMR exome
AF:
0.0932
Gnomad ASJ exome
AF:
0.0508
Gnomad EAS exome
AF:
0.228
Gnomad SAS exome
AF:
0.113
Gnomad FIN exome
AF:
0.0550
Gnomad NFE exome
AF:
0.0569
Gnomad OTH exome
AF:
0.0824
GnomAD4 exome
AF:
0.0675
AC:
97981
AN:
1451616
Hom.:
4315
Cov.:
30
AF XY:
0.0684
AC XY:
49341
AN XY:
721664
show subpopulations
Gnomad4 AFR exome
AF:
0.105
Gnomad4 AMR exome
AF:
0.0915
Gnomad4 ASJ exome
AF:
0.0480
Gnomad4 EAS exome
AF:
0.234
Gnomad4 SAS exome
AF:
0.110
Gnomad4 FIN exome
AF:
0.0554
Gnomad4 NFE exome
AF:
0.0567
Gnomad4 OTH exome
AF:
0.0779
GnomAD4 genome
AF:
0.0809
AC:
12307
AN:
152156
Hom.:
615
Cov.:
32
AF XY:
0.0824
AC XY:
6132
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.106
Gnomad4 AMR
AF:
0.0857
Gnomad4 ASJ
AF:
0.0565
Gnomad4 EAS
AF:
0.229
Gnomad4 SAS
AF:
0.102
Gnomad4 FIN
AF:
0.0580
Gnomad4 NFE
AF:
0.0569
Gnomad4 OTH
AF:
0.0974
Alfa
AF:
0.0695
Hom.:
1030
Bravo
AF:
0.0856
TwinsUK
AF:
0.0531
AC:
197
ALSPAC
AF:
0.0615
AC:
237
ESP6500AA
AF:
0.106
AC:
465
ESP6500EA
AF:
0.0550
AC:
473
ExAC
AF:
0.0856
AC:
10392
Asia WGS
AF:
0.194
AC:
674
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

CNTN3-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 18, 2019This 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
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.76
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
15
DANN
Benign
0.49
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.22
N
LIST_S2
Uncertain
0.86
D
MetaRNN
Benign
0.0015
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-2.2
N
MutationTaster
Benign
0.99
P
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.61
N
REVEL
Benign
0.19
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.015
MPC
0.19
ClinPred
0.00097
T
GERP RS
2.7
Varity_R
0.055
gMVP
0.29

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.

Other links and lift over

dbSNP: rs626578; hg19: chr3-74349062; COSMIC: COSV55166111; API