rs202095654
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_006302.3(MOGS):āc.858G>Cā(p.Gln286His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,614,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_006302.3 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MOGS | NM_006302.3 | c.858G>C | p.Gln286His | missense_variant | 4/4 | ENST00000448666.7 | NP_006293.2 | |
MOGS | NM_001146158.2 | c.540G>C | p.Gln180His | missense_variant | 5/5 | NP_001139630.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MOGS | ENST00000448666.7 | c.858G>C | p.Gln286His | missense_variant | 4/4 | 1 | NM_006302.3 | ENSP00000410992.3 |
Frequencies
GnomAD3 genomes AF: 0.000663 AC: 101AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000124 AC: 31AN: 249384Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135334
GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461822Hom.: 0 Cov.: 33 AF XY: 0.0000564 AC XY: 41AN XY: 727222
GnomAD4 genome AF: 0.000683 AC: 104AN: 152368Hom.: 0 Cov.: 33 AF XY: 0.000631 AC XY: 47AN XY: 74510
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.858G>C (p.Q286H) alteration is located in exon 4 (coding exon 4) of the MOGS gene. This alteration results from a G to C substitution at nucleotide position 858, causing the glutamine (Q) at amino acid position 286 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
MOGS-congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 08, 2024 | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 286 of the MOGS protein (p.Gln286His). This variant is present in population databases (rs202095654, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with MOGS-related conditions. ClinVar contains an entry for this variant (Variation ID: 465844). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MOGS protein function with a negative predictive value of 80%. 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. - |
MOGS-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 31, 2022 | 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