chr1-155140200-A-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_153741.2(DPM3):āc.41T>Cā(p.Leu14Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,088 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. L14Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_153741.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPM3 | NM_153741.2 | c.41T>C | p.Leu14Pro | missense_variant | 2/2 | ENST00000368400.5 | |
DPM3 | NM_018973.4 | c.131T>C | p.Leu44Pro | missense_variant | 1/1 | ||
DPM3 | XM_017001498.2 | c.41T>C | p.Leu14Pro | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPM3 | ENST00000368400.5 | c.41T>C | p.Leu14Pro | missense_variant | 2/2 | 1 | NM_153741.2 | P1 | |
DPM3 | ENST00000368399.1 | c.131T>C | p.Leu44Pro | missense_variant | 1/1 | ||||
DPM3 | ENST00000341298.3 | c.41T>C | p.Leu14Pro | missense_variant | 2/2 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249092Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134892
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727212
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74392
ClinVar
Submissions by phenotype
DPM3-congenital disorder of glycosylation Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 09, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 14 of the DPM3 protein (p.Leu14Pro). This variant is present in population databases (rs778481307, gnomAD 0.004%). ClinVar contains an entry for this variant (Variation ID: 585021). This variant is also known as p.Leu44Pro. This missense change has been observed in individual(s) with DPM3-related congenital disorder of glycosylation (PMID: 28803818, 31266720). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at