chr17-73193232-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_018714.3(COG1):c.163C>T(p.Arg55Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,608,648 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55P) has been classified as Uncertain significance.
Frequency
Consequence
NM_018714.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG1 | NM_018714.3 | c.163C>T | p.Arg55Trp | missense_variant | 1/14 | ENST00000299886.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG1 | ENST00000299886.9 | c.163C>T | p.Arg55Trp | missense_variant | 1/14 | 1 | NM_018714.3 | P1 | |
COG1 | ENST00000438720.7 | c.163C>T | p.Arg55Trp | missense_variant | 1/13 | 1 | |||
COG1 | ENST00000582587.2 | c.142C>T | p.Arg48Trp | missense_variant, NMD_transcript_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152118Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000212 AC: 5AN: 235312Hom.: 0 AF XY: 0.0000234 AC XY: 3AN XY: 128260
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1456530Hom.: 0 Cov.: 35 AF XY: 0.00000967 AC XY: 7AN XY: 724148
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152118Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
COG1 congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 28, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 55 of the COG1 protein (p.Arg55Trp). This variant is present in population databases (rs766694294, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COG1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at