20-50935136-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_003859.3(DPM1):c.779C>T(p.Thr260Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,528,576 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_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.779C>T | p.Thr260Ile | missense_variant | Exon 9 of 9 | ENST00000371588.10 | NP_003850.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000152 AC: 23AN: 151656Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000144 AC: 36AN: 250174Hom.: 0 AF XY: 0.0000888 AC XY: 12AN XY: 135196
GnomAD4 exome AF: 0.000142 AC: 195AN: 1376920Hom.: 0 Cov.: 23 AF XY: 0.000146 AC XY: 101AN XY: 690254
GnomAD4 genome AF: 0.000152 AC: 23AN: 151656Hom.: 0 Cov.: 33 AF XY: 0.000149 AC XY: 11AN XY: 74028
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation type 1E Uncertain:2
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 260 of the DPM1 protein (p.Thr260Ile). This variant is present in population databases (rs146262101, gnomAD 0.07%). 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: 338750). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
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Inborn genetic diseases Uncertain:1
The c.779C>T (p.T260I) alteration is located in exon 9 (coding exon 9) of the DPM1 gene. This alteration results from a C to T substitution at nucleotide position 779, causing the threonine (T) at amino acid position 260 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Congenital disorder of glycosylation Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at