rs35191208
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000431.4(MVK):c.769-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,595,588 control chromosomes in the GnomAD database, including 23,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.16 ( 2123 hom., cov: 33)
Exomes 𝑓: 0.17 ( 21830 hom. )
Consequence
MVK
NM_000431.4 intron
NM_000431.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.464
Genes affected
MVK (HGNC:7530): (mevalonate kinase) This gene encodes the peroxisomal enzyme mevalonate kinase. Mevalonate is a key intermediate, and mevalonate kinase a key early enzyme, in isoprenoid and sterol synthesis. Mevalonate kinase deficiency caused by mutation of this gene results in mevalonic aciduria, a disease characterized psychomotor retardation, failure to thrive, hepatosplenomegaly, anemia and recurrent febrile crises. Defects in this gene also cause hyperimmunoglobulinaemia D and periodic fever syndrome, a disorder characterized by recurrent episodes of fever associated with lymphadenopathy, arthralgia, gastrointestinal dismay and skin rash. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 12-109591203-C-T is Benign according to our data. Variant chr12-109591203-C-T is described in ClinVar as [Benign]. Clinvar id is 439922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-109591203-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MVK | NM_000431.4 | c.769-38C>T | intron_variant | ENST00000228510.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MVK | ENST00000228510.8 | c.769-38C>T | intron_variant | 1 | NM_000431.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.164 AC: 24946AN: 152136Hom.: 2127 Cov.: 33
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GnomAD3 exomes AF: 0.159 AC: 39983AN: 250774Hom.: 3270 AF XY: 0.160 AC XY: 21682AN XY: 135582
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GnomAD4 exome AF: 0.172 AC: 248041AN: 1443334Hom.: 21830 Cov.: 29 AF XY: 0.170 AC XY: 122485AN XY: 719038
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GnomAD4 genome ? AF: 0.164 AC: 24954AN: 152254Hom.: 2123 Cov.: 33 AF XY: 0.158 AC XY: 11788AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 13, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 22246419, 27884173, 27190114) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. - |
Hyperimmunoglobulin D with periodic fever;C1867981:Porokeratosis 3, disseminated superficial actinic type;C1959626:Mevalonic aciduria Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | - - |
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 12, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
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