rs151129529
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_006348.5(COG5):c.1756C>T(p.His586Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000184 in 1,562,248 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006348.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG5 | NM_006348.5 | c.1756C>T | p.His586Tyr | missense_variant | 17/22 | ENST00000297135.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG5 | ENST00000297135.9 | c.1756C>T | p.His586Tyr | missense_variant | 17/22 | 1 | NM_006348.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000753 AC: 110AN: 146118Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000238 AC: 58AN: 243846Hom.: 0 AF XY: 0.000197 AC XY: 26AN XY: 132184
GnomAD4 exome AF: 0.000124 AC: 176AN: 1416014Hom.: 1 Cov.: 27 AF XY: 0.000123 AC XY: 87AN XY: 706418
GnomAD4 genome ? AF: 0.000759 AC: 111AN: 146234Hom.: 0 Cov.: 31 AF XY: 0.000550 AC XY: 39AN XY: 70872
ClinVar
Submissions by phenotype
COG5-congenital disorder of glycosylation Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 28, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 617 of the COG5 protein (p.His617Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with COG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 487322). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | COG5: PM2, PP4:Moderate, BP4 - |
COG5-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 27, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at