rs151318611
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_032382.5(COG8):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,608,912 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_032382.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COG8 | NM_032382.5 | c.5C>T | p.Ala2Val | missense_variant | Exon 1 of 6 | ENST00000306875.10 | NP_115758.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COG8 | ENST00000306875.10 | c.5C>T | p.Ala2Val | missense_variant | Exon 1 of 6 | 1 | NM_032382.5 | ENSP00000305459.6 | ||
ENSG00000260371 | ENST00000563634.1 | c.3-2836C>T | intron_variant | Intron 1 of 2 | 4 | ENSP00000454500.1 | ||||
ENSG00000259900 | ENST00000564737.1 | n.466-2836C>T | intron_variant | Intron 3 of 4 | 5 | ENSP00000462747.1 |
Frequencies
GnomAD3 genomes AF: 0.000848 AC: 129AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000831 AC: 205AN: 246564Hom.: 0 AF XY: 0.000910 AC XY: 122AN XY: 134136
GnomAD4 exome AF: 0.00117 AC: 1705AN: 1456582Hom.: 4 Cov.: 32 AF XY: 0.00117 AC XY: 850AN XY: 724770
GnomAD4 genome AF: 0.000847 AC: 129AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000738 AC XY: 55AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:3
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COG8-congenital disorder of glycosylation Uncertain:3
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the COG8 protein (p.Ala2Val). This variant is present in population databases (rs151318611, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with COG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 377233). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at