rs181059661
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_006302.3(MOGS):c.2123G>A(p.Arg708His) 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 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R708C) has been classified as Uncertain significance.
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 | UniProt |
---|---|---|---|---|---|---|---|
MOGS | NM_006302.3 | c.2123G>A | p.Arg708His | missense_variant | 4/4 | ENST00000448666.7 | |
MOGS | NM_001146158.2 | c.1805G>A | p.Arg602His | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MOGS | ENST00000448666.7 | c.2123G>A | p.Arg708His | missense_variant | 4/4 | 1 | NM_006302.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000104 AC: 26AN: 249432Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135346
GnomAD4 exome AF: 0.0000848 AC: 124AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.0000921 AC XY: 67AN XY: 727230
GnomAD4 genome ? AF: 0.000414 AC: 63AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.000470 AC XY: 35AN XY: 74466
ClinVar
Submissions by phenotype
MOGS-congenital disorder of glycosylation Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 17, 2019 | The MOGS c.2123G>A; p.Arg708His variant (rs181059661), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 534240). This variant is found in the general population with an overall allele frequency of 0.01 % (24/ 249432 alleles) in the Genome Aggregation Database. The arginine at codon 708 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Arg708His variant is uncertain at this time. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 18, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 708 of the MOGS protein (p.Arg708His). This variant is present in population databases (rs181059661, gnomAD 0.02%). 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: 534240). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at