dbSNP rs148833471: MVD:p.Lys368Lys (chr16-88653318-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002461.3(MVD):c.1104A>G(p.Lys368Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 1,599,146 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 34)

Exomes 𝑓: 0.0074 ( 46 hom. )

Consequence

MVD
NM_002461.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.628

Variant links:

Genes affected

MVD (HGNC:7529): (mevalonate diphosphate decarboxylase) The enzyme mevalonate pyrophosphate decarboxylase catalyzes the conversion of mevalonate pyrophosphate into isopentenyl pyrophosphate in one of the early steps in cholesterol biosynthesis. It decarboxylates and dehydrates its substrate while hydrolyzing ATP. [provided by RefSeq, Jul 2008]

MVD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-88653318-T-C is Benign according to our data. Variant chr16-88653318-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 790328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.628 with no splicing effect.

BS2

High AC in GnomAd4 at 739 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVD	NM_002461.3 link	c.1104A>G	p.Lys368Lys	synonymous_variant	Exon 9 of 10	ENST00000301012.8	NP_002452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MVD	ENST00000301012.8 link	c.1104A>G	p.Lys368Lys	synonymous_variant	Exon 9 of 10	1	NM_002461.3	ENSP00000301012.3	P53602
MVD	ENST00000565149.5 link	n.1663A>G		non_coding_transcript_exon_variant	Exon 5 of 6	1
MVD	ENST00000561895.1 link	n.385A>G		non_coding_transcript_exon_variant	Exon 2 of 3	2
MVD	ENST00000562981.1 link	n.267A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00486

AC:

739

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00791

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00491

AC:

1146

AN:

233340

Hom.:

AF XY:

0.00502

AC XY:

640

AN XY:

127610

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.0000593

Gnomad SAS exome

AF:

0.00210

Gnomad FIN exome

AF:

0.00691

Gnomad NFE exome

AF:

0.00736

Gnomad OTH exome

AF:

0.00387

GnomAD4 exome

AF:

0.00741

AC:

10723

AN:

1446922

Hom.:

Cov.:

AF XY:

0.00732

AC XY:

5274

AN XY:

720102

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00306

Gnomad4 ASJ exome

AF:

0.00325

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.00230

Gnomad4 FIN exome

AF:

0.00709

Gnomad4 NFE exome

AF:

0.00865

Gnomad4 OTH exome

AF:

0.00545

GnomAD4 genome

AF:

0.00485

AC:

739

AN:

152224

Hom.:

Cov.:

AF XY:

0.00498

AC XY:

371

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00318

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.00791

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00606

Hom.:

Bravo

AF:

0.00467

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

- -

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MVD: BP4, BP7, BS2 -

Oct 05, 2017

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.89

CADD

Benign

0.32

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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