20-50935209-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003859.3(DPM1):c.706T>C(p.Tyr236His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,458,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DPM1 | NM_003859.3 | c.706T>C | p.Tyr236His | missense_variant | Exon 9 of 9 | ENST00000371588.10 | NP_003850.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251052Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135716
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1458864Hom.: 0 Cov.: 28 AF XY: 0.00000413 AC XY: 3AN XY: 725976
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.706T>C (p.Y236H) alteration is located in exon 9 (coding exon 9) of the DPM1 gene. This alteration results from a T to C substitution at nucleotide position 706, causing the tyrosine (Y) at amino acid position 236 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Congenital disorder of glycosylation type 1E Uncertain:1
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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1433475). This variant has not been reported in the literature in individuals affected with DPM1-related conditions. This variant is present in population databases (rs775589720, gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 236 of the DPM1 protein (p.Tyr236His). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at