20-50935230-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_003859.3(DPM1):āc.685A>Gā(p.Ile229Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000769 in 1,585,922 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 (ā ā ).
Frequency
Consequence
NM_003859.3 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.685A>G | p.Ile229Val | missense_variant | Exon 9 of 9 | ENST00000371588.10 | NP_003850.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000277 AC: 37AN: 133484Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000121 AC: 30AN: 248554Hom.: 0 AF XY: 0.0000967 AC XY: 13AN XY: 134428
GnomAD4 exome AF: 0.0000585 AC: 85AN: 1452346Hom.: 0 Cov.: 27 AF XY: 0.0000553 AC XY: 40AN XY: 723214
GnomAD4 genome AF: 0.000277 AC: 37AN: 133576Hom.: 0 Cov.: 33 AF XY: 0.000261 AC XY: 17AN XY: 65096
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation type 1E Uncertain:3
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 229 of the DPM1 protein (p.Ile229Val). This variant is present in population databases (rs559946698, gnomAD 0.05%). 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: 565495). 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. -
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not provided Uncertain:1
Reported as a de novo variant in an individual with schizophrenia, but additional clinical information was not included (Fromer et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25420024, 30323833, 34145229, 24463507) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at