rs779594053
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4
The NM_005677.4(COLQ):c.1195C>T(p.Arg399Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R399H) has been classified as Pathogenic.
Frequency
Consequence
NM_005677.4 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COLQ | NM_005677.4 | c.1195C>T | p.Arg399Cys | missense_variant, splice_region_variant | 15/17 | ENST00000383788.10 | |
COLQ | NM_080538.2 | c.1165C>T | p.Arg389Cys | missense_variant, splice_region_variant | 15/17 | ||
COLQ | NM_080539.4 | c.1093C>T | p.Arg365Cys | missense_variant, splice_region_variant | 14/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COLQ | ENST00000383788.10 | c.1195C>T | p.Arg399Cys | missense_variant, splice_region_variant | 15/17 | 1 | NM_005677.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251202Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135778
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461772Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 727188
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74292
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 658946). This variant has not been reported in the literature in individuals affected with COLQ-related conditions. This variant is present in population databases (rs779594053, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 399 of the COLQ protein (p.Arg399Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at