rs773281248
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_006348.5(COG5):c.1415dupC(p.Gly474TrpfsTer3) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000868 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006348.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COG5 | ENST00000297135.9 | c.1415dupC | p.Gly474TrpfsTer3 | frameshift_variant | Exon 13 of 22 | 1 | NM_006348.5 | ENSP00000297135.4 | ||
COG5 | ENST00000347053.8 | c.1415dupC | p.Gly474TrpfsTer3 | frameshift_variant | Exon 13 of 21 | 1 | ENSP00000334703.3 | |||
COG5 | ENST00000393603.7 | c.1415dupC | p.Gly474TrpfsTer3 | frameshift_variant | Exon 13 of 21 | 1 | ENSP00000377228.3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251298Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135810
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461720Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727184
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74242
ClinVar
Submissions by phenotype
COG5-congenital disorder of glycosylation Pathogenic:2
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 431150). This premature translational stop signal has been observed in individual(s) with clinical features of COG5-congenital disorder of glycosylation (PMID: 28708303). This variant is present in population databases (rs773281248, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Gly505Trpfs*3) in the COG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COG5 are known to be pathogenic (PMID: 23228021). -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at