rs61747639
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001361.5(DHODH):c.294C>T(p.Asp98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,614,168 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0031 ( 2 hom. )
Consequence
DHODH
NM_001361.5 synonymous
NM_001361.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.644
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 16-72014532-C-T is Benign according to our data. Variant chr16-72014532-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.644 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHODH | NM_001361.5 | c.294C>T | p.Asp98= | synonymous_variant | 3/9 | ENST00000219240.9 | |
DHODH | XM_047433674.1 | c.210C>T | p.Asp70= | synonymous_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHODH | ENST00000219240.9 | c.294C>T | p.Asp98= | synonymous_variant | 3/9 | 1 | NM_001361.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00218 AC: 331AN: 152164Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00215 AC: 537AN: 249580Hom.: 0 AF XY: 0.00211 AC XY: 286AN XY: 135410
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GnomAD4 exome AF: 0.00305 AC: 4466AN: 1461886Hom.: 2 Cov.: 33 AF XY: 0.00289 AC XY: 2101AN XY: 727244
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GnomAD4 genome ? AF: 0.00217 AC: 331AN: 152282Hom.: 0 Cov.: 33 AF XY: 0.00227 AC XY: 169AN XY: 74458
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Miller syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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