19-35295671-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_002361.4(MAG):c.105C>T(p.Gly35Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,612,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002361.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAG | NM_002361.4 | c.105C>T | p.Gly35Gly | synonymous_variant | Exon 4 of 11 | ENST00000392213.8 | NP_002352.1 | |
MAG | NM_001199216.2 | c.30C>T | p.Gly10Gly | synonymous_variant | Exon 4 of 11 | NP_001186145.1 | ||
MAG | NM_080600.3 | c.105C>T | p.Gly35Gly | synonymous_variant | Exon 4 of 12 | NP_542167.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000480 AC: 12AN: 249810Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135176
GnomAD4 exome AF: 0.000108 AC: 158AN: 1460082Hom.: 0 Cov.: 31 AF XY: 0.000106 AC XY: 77AN XY: 726466
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74354
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 75 Uncertain:1
This variant is present in population databases (rs143777259, gnomAD 0.008%). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 2145999). This variant has not been reported in the literature in individuals affected with MAG-related conditions. This sequence change affects codon 35 of the MAG mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MAG protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at