rs201094395
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_002361.4(MAG):c.1760G>A(p.Arg587Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,134 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R587W) has been classified as Uncertain significance.
Frequency
Consequence
NM_002361.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAG | NM_002361.4 | c.1760G>A | p.Arg587Gln | missense_variant | 11/11 | ENST00000392213.8 | |
MAG | NM_001199216.2 | c.1685G>A | p.Arg562Gln | missense_variant | 11/11 | ||
MAG | NM_080600.3 | c.*56G>A | 3_prime_UTR_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAG | ENST00000392213.8 | c.1760G>A | p.Arg587Gln | missense_variant | 11/11 | 1 | NM_002361.4 | P1 | |
MAG | ENST00000537831.2 | c.1685G>A | p.Arg562Gln | missense_variant | 11/11 | 1 | |||
MAG | ENST00000361922.8 | c.*56G>A | 3_prime_UTR_variant | 12/12 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251080Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135734
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461786Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727204
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152348Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74492
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 75 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 28, 2018 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MAG-related disease. This variant is present in population databases (rs201094395, ExAC 0.02%). This sequence change replaces arginine with glutamine at codon 587 of the MAG protein (p.Arg587Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at