chr16-72017043-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001361.5(DHODH):c.454G>A(p.Gly152Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,613,816 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 Uncertain significance (★★).
Frequency
Consequence
NM_001361.5 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 |
---|---|---|---|---|---|---|---|---|
DHODH | NM_001361.5 | c.454G>A | p.Gly152Arg | missense_variant | Exon 4 of 9 | ENST00000219240.9 | NP_001352.2 | |
DHODH | XM_047433674.1 | c.370G>A | p.Gly124Arg | missense_variant | Exon 4 of 9 | XP_047289630.1 | ||
DHODH | XM_005255829.5 | c.25G>A | p.Gly9Arg | missense_variant | Exon 2 of 7 | XP_005255886.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152018Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000761 AC: 19AN: 249544Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135400
GnomAD4 exome AF: 0.000151 AC: 221AN: 1461798Hom.: 0 Cov.: 32 AF XY: 0.000142 AC XY: 103AN XY: 727206
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74252
ClinVar
Submissions by phenotype
Miller syndrome Pathogenic:1
- -
not provided Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 152 of the DHODH protein (p.Gly152Arg). This variant is present in population databases (rs267606766, gnomAD 0.01%). This missense change has been observed in individual(s) with Miller syndrome (PMID: 19915526, 20220176). It has also been observed to segregate with disease in related individuals. This variant is also known as chr16:70608443 G>R. ClinVar contains an entry for this variant (Variation ID: 16803). 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 disruptive. Experimental studies have shown that this missense change affects DHODH function (PMID: 22692683, 22967083). 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