rs759911990
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005677.4(COLQ):c.788_789insC(p.Pro265AlafsTer37) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P263P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005677.4 frameshift
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.788_789insC | p.Pro265AlafsTer37 | frameshift_variant | 12/17 | ENST00000383788.10 | |
COLQ | NM_080538.2 | c.758_759insC | p.Pro255AlafsTer37 | frameshift_variant | 12/17 | ||
COLQ | NM_080539.4 | c.686_687insC | p.Pro231AlafsTer37 | frameshift_variant | 11/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COLQ | ENST00000383788.10 | c.788_789insC | p.Pro265AlafsTer37 | frameshift_variant | 12/17 | 1 | NM_005677.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247494Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134338
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461730Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727158
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 5 Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 05, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 6653). This premature translational stop signal has been observed in individual(s) with clinical features of COLQ-related conditions (PMID: 9689136, 28024842). This variant is present in population databases (rs759911990, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Pro265Alafs*37) 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 | Oct 05, 2023 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 04, 1998 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at