rs1555201269
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_001843.4(CNTN1):c.2795C>A(p.Ser932Ter) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CNTN1
NM_001843.4 stop_gained
NM_001843.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 4.89
Genes affected
CNTN1 (HGNC:2171): (contactin 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. It 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. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 12-41027941-C-A is Pathogenic according to our data. Variant chr12-41027941-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 469421.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTN1 | NM_001843.4 | c.2795C>A | p.Ser932Ter | stop_gained | 22/24 | ENST00000551295.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN1 | ENST00000551295.7 | c.2795C>A | p.Ser932Ter | stop_gained | 22/24 | 1 | NM_001843.4 | P3 | |
CNTN1 | ENST00000347616.5 | c.2795C>A | p.Ser932Ter | stop_gained | 21/23 | 1 | P3 | ||
CNTN1 | ENST00000348761.2 | c.2762C>A | p.Ser921Ter | stop_gained | 20/22 | 1 | A1 | ||
CNTN1 | ENST00000550305.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1456298Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 724968
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1456298
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
724968
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Compton-North congenital myopathy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 25, 2021 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CNTN1 are known to be pathogenic (PMID: 19026398, 22242131). This variant has not been reported in the literature in individuals with CNTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 469421). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser932*) in the CNTN1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 28
Find out detailed SpliceAI scores and Pangolin per-transcript scores at