rs375580399
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_002225.5(IVD):c.822C>T(p.Tyr274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
IVD
NM_002225.5 synonymous
NM_002225.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.891
Genes affected
IVD (HGNC:6186): (isovaleryl-CoA dehydrogenase) Isovaleryl-CoA dehydrogenase (IVD) is a mitochondrial matrix enzyme that catalyzes the third step in leucine catabolism. The genetic deficiency of IVD results in an accumulation of isovaleric acid, which is toxic to the central nervous system and leads to isovaleric acidemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
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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;
BP6
?
Variant 15-40414926-C-T is Benign according to our data. Variant chr15-40414926-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 529436.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IVD | NM_002225.5 | c.822C>T | p.Tyr274= | synonymous_variant | 8/12 | ENST00000487418.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IVD | ENST00000487418.8 | c.822C>T | p.Tyr274= | synonymous_variant | 8/12 | 1 | NM_002225.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251326Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135838
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461796Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727196
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Isovaleryl-CoA dehydrogenase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
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Benign
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Benign
RBP_binding_hub_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -37
Find out detailed SpliceAI scores and Pangolin per-transcript scores at