chr16-72012233-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001361.5(DHODH):c.205C>T(p.Arg69Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000080 ( 1 hom. )
Consequence
DHODH
NM_001361.5 missense
NM_001361.5 missense
Scores
8
6
Clinical Significance
Conservation
PhyloP100: 1.75
Genes affected
DHODH (HGNC:2867): (dihydroorotate dehydrogenase (quinone)) The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis. This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.13202158).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHODH | NM_001361.5 | c.205C>T | p.Arg69Trp | missense_variant | 2/9 | ENST00000219240.9 | |
DHODH | XM_047433674.1 | c.121C>T | p.Arg41Trp | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHODH | ENST00000219240.9 | c.205C>T | p.Arg69Trp | missense_variant | 2/9 | 1 | NM_001361.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152140Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000156 AC: 39AN: 249516Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135368
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GnomAD4 exome AF: 0.0000800 AC: 117AN: 1461870Hom.: 1 Cov.: 32 AF XY: 0.000102 AC XY: 74AN XY: 727240
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74422
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2022 | 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 tolerated. 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. This variant has not been reported in the literature in individuals affected with DHODH-related conditions. This variant is present in population databases (rs201823503, gnomAD 0.07%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 69 of the DHODH protein (p.Arg69Trp). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Sift4G
Uncertain
D;D;D
Polyphen
0.99
.;D;.
Vest4
MVP
MPC
0.29
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at