Variant 12-109573660-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.87

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=-0.73).

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 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MVK	XM_017019313.3 linkuse as main transcript	c.-15+89G>A		intron_variant
MVK	XM_047428873.1 linkuse as main transcript	c.286+89G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Appris
MVK	ENST00000539335.5 linkuse as main transcript	c.-6+89G>A	intron_variant	3
MVK	ENST00000546277.6 linkuse as main transcript	c.-15+89G>A	intron_variant	5	P1
MVK	ENST00000535044.1 linkuse as main transcript	n.231+89G>A	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

1068

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00634

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00526

GnomAD4 exome

AF:

0.00887

AC:

5370

AN:

605422

Hom.:

Cov.:

AF XY:

0.00841

AC XY:

2684

AN XY:

319150

show subpopulations

Gnomad4 AFR exome

AF:

0.00202

Gnomad4 AMR exome

AF:

0.00482

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0000313

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.00841

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00942

GnomAD4 genome

AF:

0.00701

AC:

1068

AN:

152360

Hom.:

Cov.:

AF XY:

0.00687

AC XY:

512

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00753

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00603

Hom.:

Bravo

AF:

0.00663

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.92

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