rs2270374

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000431.4(MVK):c.885+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,601,586 control chromosomes in the GnomAD database, including 22,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1484 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21297 hom. )

Consequence

MVK
NM_000431.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.45

Publications

15 publications found

Variant links:

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]

MVK Gene-Disease associations (from GenCC):

porokeratosis 3, disseminated superficial actinic type
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
hyperimmunoglobulinemia D with periodic fever
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
mevalonate kinase deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mevalonic aciduria
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
disseminated superficial actinic porokeratosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
porokeratosis of Mibelli
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MVK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-109591381-G-A is Benign according to our data. Variant chr12-109591381-G-A is described in ClinVar as Benign. ClinVar VariationId is 439923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000431.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MVK	NM_000431.4	MANE Select	c.885+24G>A	intron	N/A	NP_000422.1	Q03426
MVK	NM_001414512.1		c.960+24G>A	intron	N/A	NP_001401441.1
MVK	NM_001114185.3		c.885+24G>A	intron	N/A	NP_001107657.1	B2RDU6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MVK	ENST00000228510.8	TSL:1 MANE Select	c.885+24G>A	intron	N/A	ENSP00000228510.3	Q03426
MVK	ENST00000546277.6	TSL:5	c.885+24G>A	intron	N/A	ENSP00000438153.2	Q03426
MVK	ENST00000878306.1		c.885+24G>A	intron	N/A	ENSP00000548365.1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19106

AN:

152194

Hom.:

1488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.143

GnomAD2 exomes

AF:

0.149

AC:

37314

AN:

249608

AF XY:

0.152

show subpopulations

Gnomad AFR exome

AF:

0.0342

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.168

AC:

243852

AN:

1449274

Hom.:

21297

Cov.:

AF XY:

0.167

AC XY:

120763

AN XY:

721800

show subpopulations

African (AFR)

AF:

0.0309

AC:

1025

AN:

33158

American (AMR)

AF:

0.135

AC:

6040

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

4955

AN:

26060

East Asian (EAS)

AF:

0.160

AC:

6342

AN:

39614

South Asian (SAS)

AF:

0.138

AC:

11880

AN:

86018

European-Finnish (FIN)

AF:

0.108

AC:

5678

AN:

52666

Middle Eastern (MID)

AF:

0.186

AC:

1066

AN:

5742

European-Non Finnish (NFE)

AF:

0.179

AC:

197103

AN:

1101294

Other (OTH)

AF:

0.163

AC:

9763

AN:

60036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

10368

20737

31105

41474

51842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6866

13732

20598

27464

34330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.125

AC:

19104

AN:

152312

Hom.:

1484

Cov.:

AF XY:

0.122

AC XY:

9052

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0352

AC:

1463

AN:

41562

American (AMR)

AF:

0.140

AC:

2137

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3470

East Asian (EAS)

AF:

0.141

AC:

729

AN:

5180

South Asian (SAS)

AF:

0.129

AC:

624

AN:

4828

European-Finnish (FIN)

AF:

0.0987

AC:

1048

AN:

10620

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11883

AN:

68028

Other (OTH)

AF:

0.146

AC:

309

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

866

1732

2599

3465

4331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.153

Hom.:

751

Bravo

AF:

0.127

Asia WGS

AF:

0.143

AC:

498

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0010

(source)

DANN

Benign

0.45

PhyloP100

-3.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over