rs775143571
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_000744.7(CHRNA4):c.176C>T(p.Ser59Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,620 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S59S) has been classified as Likely benign.
Frequency
Consequence
NM_000744.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.176C>T | p.Ser59Leu | missense_variant | 2/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.-371C>T | 5_prime_UTR_variant | 2/6 | |||
CHRNA4 | NR_046317.2 | n.360C>T | non_coding_transcript_exon_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.176C>T | p.Ser59Leu | missense_variant | 2/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249856Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135654
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460372Hom.: 0 Cov.: 37 AF XY: 0.00000688 AC XY: 5AN XY: 726476
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74382
ClinVar
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 24, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 577643). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. This variant is present in population databases (rs775143571, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 59 of the CHRNA4 protein (p.Ser59Leu). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | CHRNA4: PM2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at