chr17-73193233-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_018714.3(COG1):āc.164G>Cā(p.Arg55Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000572 in 1,608,770 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55W) has been classified as Uncertain significance.
Frequency
Consequence
NM_018714.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG1 | NM_018714.3 | c.164G>C | p.Arg55Pro | missense_variant | 1/14 | ENST00000299886.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG1 | ENST00000299886.9 | c.164G>C | p.Arg55Pro | missense_variant | 1/14 | 1 | NM_018714.3 | P1 | |
COG1 | ENST00000438720.7 | c.164G>C | p.Arg55Pro | missense_variant | 1/13 | 1 | |||
COG1 | ENST00000582587.2 | c.143G>C | p.Arg48Pro | missense_variant, NMD_transcript_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000212 AC: 5AN: 235376Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 128258
GnomAD4 exome AF: 0.0000584 AC: 85AN: 1456636Hom.: 0 Cov.: 35 AF XY: 0.0000497 AC XY: 36AN XY: 724210
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74310
ClinVar
Submissions by phenotype
COG1 congenital disorder of glycosylation Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 30, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2021 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 55 of the COG1 protein (p.Arg55Pro). This variant is present in population databases (rs751859972, gnomAD 0.005%). 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