11-99556237-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014361.4(CNTN5):​c.23T>A​(p.Met8Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000027 in 1,518,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CNTN5
NM_014361.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96
Variant links:
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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041709602).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNTN5NM_014361.4 linkuse as main transcriptc.23T>A p.Met8Lys missense_variant 3/25 ENST00000524871.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNTN5ENST00000524871.6 linkuse as main transcriptc.23T>A p.Met8Lys missense_variant 3/251 NM_014361.4 P1O94779-1

Frequencies

GnomAD3 genomes
AF:
0.000178
AC:
27
AN:
151690
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000604
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:
0.000959
GnomAD3 exomes
AF:
0.0000469
AC:
7
AN:
149354
Hom.:
0
AF XY:
0.0000126
AC XY:
1
AN XY:
79054
show subpopulations
Gnomad AFR exome
AF:
0.000875
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.0000102
AC:
14
AN:
1366584
Hom.:
0
Cov.:
27
AF XY:
0.00000594
AC XY:
4
AN XY:
673504
show subpopulations
Gnomad4 AFR exome
AF:
0.000452
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000178
AC:
27
AN:
151690
Hom.:
0
Cov.:
31
AF XY:
0.000135
AC XY:
10
AN XY:
74088
show subpopulations
Gnomad4 AFR
AF:
0.000604
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000959
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000223
ExAC
AF:
0.0000284
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 18, 2024The c.23T>A (p.M8K) alteration is located in exon 1 (coding exon 1) of the CNTN5 gene. This alteration results from a T to A substitution at nucleotide position 23, causing the methionine (M) at amino acid position 8 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
19
DANN
Benign
0.91
DEOGEN2
Benign
0.11
.;T;T;.
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.38
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.66
T;.;T;T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.042
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;N;N;N
MutationTaster
Benign
0.99
N;N;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.18
N;N;N;N
REVEL
Benign
0.10
Sift
Uncertain
0.0090
D;D;D;D
Sift4G
Uncertain
0.019
D;D;D;D
Polyphen
0.0010
.;B;B;B
Vest4
0.30
MVP
0.61
MPC
0.047
ClinPred
0.070
T
GERP RS
4.7
Varity_R
0.53
gMVP
0.61

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: rs781294747; hg19: chr11-99426968; API