20-50948650-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_003859.3(DPM1):āc.274C>Gā(p.Arg92Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,660 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 Pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R92Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_003859.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.274C>G | p.Arg92Gly | missense_variant | 3/9 | ENST00000371588.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPM1 | ENST00000371588.10 | c.274C>G | p.Arg92Gly | missense_variant | 3/9 | 1 | NM_003859.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152040Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251480Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135914
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461620Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727120
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5AN XY: 74236
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation type 1E Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2023 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects DPM1 function (PMID: 10642602). 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. ClinVar contains an entry for this variant (Variation ID: 6296). This missense change has been observed in individual(s) with congenital disorder of glycosylation (PMID: 10642597, 10642602, 27481510). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121908583, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 92 of the DPM1 protein (p.Arg92Gly). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2000 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at