rs767086250
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001843.4(CNTN1):c.1814G>A(p.Gly605Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G605S) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTN1 | NM_001843.4 | c.1814G>A | p.Gly605Asp | missense_variant | 16/24 | ENST00000551295.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN1 | ENST00000551295.7 | c.1814G>A | p.Gly605Asp | missense_variant | 16/24 | 1 | NM_001843.4 | P3 | |
CNTN1 | ENST00000347616.5 | c.1814G>A | p.Gly605Asp | missense_variant | 15/23 | 1 | P3 | ||
CNTN1 | ENST00000348761.2 | c.1781G>A | p.Gly594Asp | missense_variant | 14/22 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250780Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135496
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461612Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727100
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 03, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2023 | The c.1814G>A (p.G605D) alteration is located in exon 16 (coding exon 15) of the CNTN1 gene. This alteration results from a G to A substitution at nucleotide position 1814, causing the glycine (G) at amino acid position 605 to be replaced by an aspartic acid (D). 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 | Nov 01, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 605 of the CNTN1 protein (p.Gly605Asp). This variant is present in population databases (rs767086250, gnomAD no frequency). 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: 434797). 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. 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