chr3-15466437-C-A
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3PP5_Moderate
The NM_005677.4(COLQ):c.718G>T(p.Gly240Ter) variant causes a stop gained, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,459,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005677.4 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COLQ | NM_005677.4 | c.718G>T | p.Gly240Ter | stop_gained, splice_region_variant | 12/17 | ENST00000383788.10 | |
COLQ | NM_080538.2 | c.688G>T | p.Gly230Ter | stop_gained, splice_region_variant | 12/17 | ||
COLQ | NM_080539.4 | c.616G>T | p.Gly206Ter | stop_gained, splice_region_variant | 11/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COLQ | ENST00000383788.10 | c.718G>T | p.Gly240Ter | stop_gained, splice_region_variant | 12/17 | 1 | NM_005677.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248098Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134480
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459972Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726402
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 5 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 26, 2002 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 11, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 6657). This premature translational stop signal has been observed in individual(s) with congenital myasthenic syndrome (PMID: 11865139, 28024842). This variant is present in population databases (rs104893735, gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly240*) 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at