chr20-50935173-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_003859.3(DPM1):āc.742T>Cā(p.Ser248Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,456,680 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 Likely pathogenic (ā ).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.742T>C | p.Ser248Pro | missense_variant | Exon 9 of 9 | ENST00000371588.10 | NP_003850.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1456680Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 725124
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation type 1E Pathogenic:2
The DPM1 c.847T>C (p.Ser283Pro) variant, also known as c.742T>C (p.Ser248Pro), is a missense variant that has been reported in at least two studies and is found in four individuals with congenital disorder of glycosylation, including in three in a homozygous state and one in a compound heterozygous state (Garcia-Silva et al. 2004; Medrano et al. 2019). This variant is not found in the Genome Aggregation Database, version 2.1.1 and version 3.1.1, and is in a region of good sequencing coverage, so the variant is presumed to be rare. Analysis of the p.Ser283Pro variant in knockdown zebrafish found that the variant partially reduced DPM1 function, which authors suggest is consistent with a milder phenotype (Ardiccioni et al. 2015). Based on the evidence, the p.Ser283Pro variant is classified as likely pathogenic for congenital disorder of glycosylation. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at