rs41276187
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006348.5(COG5):āc.1247A>Gā(p.Tyr416Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0062 in 1,613,714 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG5 | NM_006348.5 | c.1247A>G | p.Tyr416Cys | missense_variant | 12/22 | ENST00000297135.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG5 | ENST00000297135.9 | c.1247A>G | p.Tyr416Cys | missense_variant | 12/22 | 1 | NM_006348.5 | P2 | |
COG5 | ENST00000347053.8 | c.1247A>G | p.Tyr416Cys | missense_variant | 12/21 | 1 | A2 | ||
COG5 | ENST00000393603.7 | c.1247A>G | p.Tyr416Cys | missense_variant | 12/21 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00517 AC: 786AN: 152154Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.00474 AC: 1192AN: 251284Hom.: 4 AF XY: 0.00478 AC XY: 649AN XY: 135824
GnomAD4 exome AF: 0.00631 AC: 9222AN: 1461442Hom.: 39 Cov.: 30 AF XY: 0.00620 AC XY: 4509AN XY: 727048
GnomAD4 genome ? AF: 0.00516 AC: 786AN: 152272Hom.: 4 Cov.: 32 AF XY: 0.00493 AC XY: 367AN XY: 74470
ClinVar
Submissions by phenotype
COG5-congenital disorder of glycosylation Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Uncertain significance, 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, 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. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 05, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 27, 2016 | 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. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | COG5: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 12, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at