rs35191208

Variant names:

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.464

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 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
MVK	NM_000431.4 link	c.769-38C>T		intron_variant	Intron 8 of 10	ENST00000228510.8	NP_000422.1	Q03426B2RDU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVK	ENST00000228510.8 link	c.769-38C>T		intron_variant	Intron 8 of 10	1	NM_000431.4	ENSP00000228510.3		Q03426

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24946

AN:

152136

Hom.:

2127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0987

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.159

AC:

39983

AN:

250774

Hom.:

3270

AF XY:

0.160

AC XY:

21682

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.172

AC:

248041

AN:

1443334

Hom.:

21830

Cov.:

AF XY:

0.170

AC XY:

122485

AN XY:

719038

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.164

AC:

24954

AN:

152254

Hom.:

2123

Cov.:

AF XY:

0.158

AC XY:

11788

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.141

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0987

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.175

Hom.:

436

Bravo

AF:

0.170

Asia WGS

AF:

0.150

AC:

520

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 13, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22246419, 27884173, 27190114) -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autoinflammatory syndrome

Benign:1

Dec 12, 2016

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.4

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over