rs370745426
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000431.4(MVK):c.618T>A(p.Ala206=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,570 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00020 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
MVK
NM_000431.4 synonymous
NM_000431.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.39
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant 12-109586112-T-A is Benign according to our data. Variant chr12-109586112-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 515729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.39 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MVK | NM_000431.4 | c.618T>A | p.Ala206= | synonymous_variant | 6/11 | ENST00000228510.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MVK | ENST00000228510.8 | c.618T>A | p.Ala206= | synonymous_variant | 6/11 | 1 | NM_000431.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152258Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251300Hom.: 1 AF XY: 0.0000736 AC XY: 10AN XY: 135844
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461312Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727036
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GnomAD4 genome ? AF: 0.000204 AC: 31AN: 152258Hom.: 1 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74382
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hyperimmunoglobulin D with periodic fever;C1867981:Porokeratosis 3, disseminated superficial actinic type;C1959626:Mevalonic aciduria Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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