rs66486014
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000546277.6(MVK):c.-15+89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 757,782 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0070 ( 6 hom., cov: 33)
Exomes 𝑓: 0.0089 ( 36 hom. )
Consequence
MVK
ENST00000546277.6 intron
ENST00000546277.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.87
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=-0.73).
BP6
?
Variant 12-109573660-G-A is Benign according to our data. Variant chr12-109573660-G-A is described in ClinVar as [Benign]. Clinvar id is 534562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00701 (1068/152360) while in subpopulation NFE AF= 0.0103 (704/68028). AF 95% confidence interval is 0.00971. There are 6 homozygotes in gnomad4. There are 512 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MVK | XM_017019313.3 | c.-15+89G>A | intron_variant | ||||
MVK | XM_047428873.1 | c.286+89G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MVK | ENST00000539335.5 | c.-6+89G>A | intron_variant | 3 | |||||
MVK | ENST00000546277.6 | c.-15+89G>A | intron_variant | 5 | P1 | ||||
MVK | ENST00000535044.1 | n.231+89G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00702 AC: 1068AN: 152242Hom.: 6 Cov.: 33
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GnomAD4 exome AF: 0.00887 AC: 5370AN: 605422Hom.: 36 Cov.: 7 AF XY: 0.00841 AC XY: 2684AN XY: 319150
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GnomAD4 genome ? AF: 0.00701 AC: 1068AN: 152360Hom.: 6 Cov.: 33 AF XY: 0.00687 AC XY: 512AN XY: 74504
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Methylmalonic aciduria, cblB type Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 19, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | MMAB: BS1, BS2; MVK: BS1, BS2 - |
Computational scores
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Name
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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