rs201778720
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001843.4(CNTN1):c.3037C>A(p.Leu1013Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. L1013F) has been classified as Uncertain significance.
Frequency
Consequence
NM_001843.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTN1 | NM_001843.4 | c.3037C>A | p.Leu1013Ile | missense_variant | 24/24 | ENST00000551295.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN1 | ENST00000551295.7 | c.3037C>A | p.Leu1013Ile | missense_variant | 24/24 | 1 | NM_001843.4 | P3 | |
CNTN1 | ENST00000347616.5 | c.3037C>A | p.Leu1013Ile | missense_variant | 23/23 | 1 | P3 | ||
CNTN1 | ENST00000348761.2 | c.3004C>A | p.Leu1002Ile | missense_variant | 22/22 | 1 | A1 | ||
CNTN1 | ENST00000548481.1 | c.*112C>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251324Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135838
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461754Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727186
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2021 | The c.3037C>A (p.L1013I) alteration is located in exon 24 (coding exon 23) of the CNTN1 gene. This alteration results from a C to A substitution at nucleotide position 3037, causing the leucine (L) at amino acid position 1013 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Compton-North congenital myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1013 of the CNTN1 protein (p.Leu1013Ile). This variant is present in population databases (rs201778720, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CNTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2245608). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CNTN1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at