rs142433421
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006348.5(COG5):āc.1826T>Cā(p.Ile609Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000463 in 1,612,088 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I609I) has been classified as Benign.
Frequency
Consequence
NM_006348.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG5 | NM_006348.5 | c.1826T>C | p.Ile609Thr | missense_variant | 17/22 | ENST00000297135.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG5 | ENST00000297135.9 | c.1826T>C | p.Ile609Thr | missense_variant | 17/22 | 1 | NM_006348.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000771 AC: 117AN: 151778Hom.: 2 Cov.: 31
GnomAD3 exomes AF: 0.00189 AC: 474AN: 251334Hom.: 10 AF XY: 0.00174 AC XY: 237AN XY: 135846
GnomAD4 exome AF: 0.000431 AC: 629AN: 1460184Hom.: 9 Cov.: 30 AF XY: 0.000401 AC XY: 291AN XY: 726464
GnomAD4 genome ? AF: 0.000770 AC: 117AN: 151904Hom.: 2 Cov.: 31 AF XY: 0.000822 AC XY: 61AN XY: 74242
ClinVar
Submissions by phenotype
COG5-congenital disorder of glycosylation Uncertain:1Benign:3
Benign, criteria provided, single submitter | clinical testing | Mendelics | Aug 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 2.4% East Asian population in ExAC - |
COG5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 2019 | 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