rs150351852
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_006348.5(COG5):c.298C>T(p.Leu100Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000858 in 1,613,628 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts 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
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000927 AC: 141AN: 152168Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000843 AC: 212AN: 251422Hom.: 1 AF XY: 0.000854 AC XY: 116AN XY: 135880
GnomAD4 exome AF: 0.000851 AC: 1244AN: 1461342Hom.: 1 Cov.: 31 AF XY: 0.000845 AC XY: 614AN XY: 727018
GnomAD4 genome AF: 0.000926 AC: 141AN: 152286Hom.: 1 Cov.: 32 AF XY: 0.00102 AC XY: 76AN XY: 74472
ClinVar
Submissions by phenotype
COG5-congenital disorder of glycosylation Uncertain:4Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
- -
- -
- -
The heterozygous p.Leu131Phe (p.Leu100Phe) variant in COG5 was identified by our study in the compound heterozygous state, along with a likely benign variant, in 1 individual with congenital disorder of glycosylation, type IIi (commonly referred to as COG5-CDG or CDG2I). The variant has not been previously reported in individuals with COG5-CDG and has been identified in 0.21% (76/35438) of Latino chromosomes and 1 homozygote by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs150351852). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. The p.Leu131Phe variant is located in a region of COG5 that is essential to protein folding and stability, suggesting that this variant is in a functional domain and slightly supports pathogenicity (PMID: 25331899). In summary, the clinical significance of the variant is uncertain. ACMG/AMP Criteria applied: BS1, PM1 (Richards 2015). -
not provided Uncertain:1
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at