rs770045897
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005677.4(COLQ):c.679C>T(p.Arg227Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,898 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005677.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COLQ | NM_005677.4 | c.679C>T | p.Arg227Ter | stop_gained | 11/17 | ENST00000383788.10 | |
COLQ | NM_080538.2 | c.649C>T | p.Arg217Ter | stop_gained | 11/17 | ||
COLQ | NM_080539.4 | c.577C>T | p.Arg193Ter | stop_gained | 10/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COLQ | ENST00000383788.10 | c.679C>T | p.Arg227Ter | stop_gained | 11/17 | 1 | NM_005677.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251472Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461806Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727196
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 5 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280125). This premature translational stop signal has been observed in individual(s) with congenital myasthenic syndrome (PMID: 18180250, 22088788, 23553736, 25557462). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs770045897, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg227*) in the COLQ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COLQ are known to be pathogenic (PMID: 22678886). - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 26, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Dec 18, 2017 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 13, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 23553736, 22088788, 28464723, 25557462, 18180250) - |
Synaptic congenital myasthenic syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences | Jan 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at