20-50935161-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003859.3(DPM1):c.754G>A(p.Gly252Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,602,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003859.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.754G>A | p.Gly252Arg | missense_variant | Exon 9 of 9 | ENST00000371588.10 | NP_003850.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151592Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000289 AC: 42AN: 1451272Hom.: 0 Cov.: 28 AF XY: 0.0000249 AC XY: 18AN XY: 722868
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151592Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 73982
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation type 1E Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 252 of the DPM1 protein (p.Gly252Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DPM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 850062). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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