rs566695601
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001843.4(CNTN1):āc.2284C>Gā(p.Pro762Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,966 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P762R) 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.2284C>G | p.Pro762Ala | missense_variant | 19/24 | ENST00000551295.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN1 | ENST00000551295.7 | c.2284C>G | p.Pro762Ala | missense_variant | 19/24 | 1 | NM_001843.4 | P3 | |
CNTN1 | ENST00000347616.5 | c.2284C>G | p.Pro762Ala | missense_variant | 18/23 | 1 | P3 | ||
CNTN1 | ENST00000348761.2 | c.2251C>G | p.Pro751Ala | missense_variant | 17/22 | 1 | A1 | ||
CNTN1 | ENST00000550305.1 | n.243C>G | non_coding_transcript_exon_variant | 3/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461814Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727204
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2022 | The c.2284C>G (p.P762A) alteration is located in exon 19 (coding exon 18) of the CNTN1 gene. This alteration results from a C to G substitution at nucleotide position 2284, causing the proline (P) at amino acid position 762 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 29, 2018 | A variant of uncertain significance has been identified in the CNTN1 gene. The P762A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P762A variant is observed in 1/8726 (0.01%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The P762A variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at