11-99819736-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_014361.4(CNTN5):c.248A>G(p.Tyr83Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000056 in 1,606,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y83H) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 54)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
CNTN5
NM_014361.4 missense
NM_014361.4 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 4.62
Publications
0 publications found
Genes affected
CNTN5 (HGNC:2175): (contactin 5) The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152290Hom.: 0 Cov.: 54 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152290
Hom.:
Cov.:
54
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000128 AC: 3AN: 233570 AF XY: 0.0000157 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
233570
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000481 AC: 7AN: 1453826Hom.: 0 Cov.: 51 AF XY: 0.00000553 AC XY: 4AN XY: 722754 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
7
AN:
1453826
Hom.:
Cov.:
51
AF XY:
AC XY:
4
AN XY:
722754
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33392
American (AMR)
AF:
AC:
4
AN:
42796
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26038
East Asian (EAS)
AF:
AC:
0
AN:
39366
South Asian (SAS)
AF:
AC:
0
AN:
85734
European-Finnish (FIN)
AF:
AC:
0
AN:
51962
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1108566
Other (OTH)
AF:
AC:
0
AN:
60212
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.318
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000131 AC: 2AN: 152290Hom.: 0 Cov.: 54 AF XY: 0.0000269 AC XY: 2AN XY: 74398 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
152290
Hom.:
Cov.:
54
AF XY:
AC XY:
2
AN XY:
74398
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41486
American (AMR)
AF:
AC:
1
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10632
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68058
Other (OTH)
AF:
AC:
1
AN:
2094
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.002339), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Nov 09, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.248A>G (p.Y83C) alteration is located in exon 1 (coding exon 1) of the CNTN5 gene. This alteration results from a A to G substitution at nucleotide position 248, causing the tyrosine (Y) at amino acid position 83 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;.;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Uncertain
D;D;D;.
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;D;D;.
Vest4
MutPred
Loss of phosphorylation at Y83 (P = 0.0367);Loss of phosphorylation at Y83 (P = 0.0367);Loss of phosphorylation at Y83 (P = 0.0367);.;
MVP
MPC
0.24
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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