20-50935152-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003859.3(DPM1):āc.763A>Gā(p.Thr255Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,592,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_003859.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.763A>G | p.Thr255Ala | missense_variant | Exon 9 of 9 | ENST00000371588.10 | NP_003850.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000661 AC: 1AN: 151192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250788Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135574
GnomAD4 exome AF: 0.0000118 AC: 17AN: 1441604Hom.: 0 Cov.: 27 AF XY: 0.0000153 AC XY: 11AN XY: 718702
GnomAD4 genome AF: 0.00000661 AC: 1AN: 151192Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1AN XY: 73782
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.763A>G (p.T255A) alteration is located in exon 9 (coding exon 9) of the DPM1 gene. This alteration results from a A to G substitution at nucleotide position 763, causing the threonine (T) at amino acid position 255 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Congenital disorder of glycosylation type 1E Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 255 of the DPM1 protein (p.Thr255Ala). This variant is present in population databases (rs748394583, gnomAD 0.002%). 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: 650050). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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