Variant 16-88653352-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002461.3(MVD):c.1070C>T(p.Ala357Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00404 in 1,596,464 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0042 ( 21 hom. )

Consequence

MVD
NM_002461.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.54

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007250488).

BP6

Variant 16-88653352-G-A is Benign according to our data. Variant chr16-88653352-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2498675.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00417 (6016/1444214) while in subpopulation AMR AF= 0.0064 (246/38438). AF 95% confidence interval is 0.00574. There are 21 homozygotes in gnomad4_exome. There are 2925 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 441 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MVD	NM_002461.3 linkuse as main transcript	c.1070C>T	p.Ala357Val	missense_variant	9/10	ENST00000301012.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MVD	ENST00000301012.8 linkuse as main transcript	c.1070C>T	p.Ala357Val	missense_variant	9/10	1	NM_002461.3	P1
MVD	ENST00000565149.5 linkuse as main transcript	n.1629C>T		non_coding_transcript_exon_variant	5/6	1
MVD	ENST00000561895.1 linkuse as main transcript	n.351C>T		non_coding_transcript_exon_variant	2/3	2
MVD	ENST00000562981.1 linkuse as main transcript	n.233C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

441

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00466

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00379

AC:

876

AN:

230888

Hom.:

AF XY:

0.00391

AC XY:

494

AN XY:

126340

show subpopulations

Gnomad AFR exome

AF:

0.000784

Gnomad AMR exome

AF:

0.00648

Gnomad ASJ exome

AF:

0.00329

Gnomad EAS exome

AF:

0.0000598

Gnomad SAS exome

AF:

0.000537

Gnomad FIN exome

AF:

0.000426

Gnomad NFE exome

AF:

0.00559

Gnomad OTH exome

AF:

0.00502

GnomAD4 exome

AF:

0.00417

AC:

6016

AN:

1444214

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

2925

AN XY:

718852

show subpopulations

Gnomad4 AFR exome

AF:

0.00103

Gnomad4 AMR exome

AF:

0.00640

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.000384

Gnomad4 NFE exome

AF:

0.00483

Gnomad4 OTH exome

AF:

0.00394

GnomAD4 genome

AF:

0.00290

AC:

441

AN:

152250

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00466

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00426

Hom.:

Bravo

AF:

0.00325

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00351

AC:

426

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

MVD: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.15

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.55

REVEL

Benign

0.039

Sift

Benign

0.32

Sift4G

Benign

0.33

Polyphen

0.0040

Vest4

0.16

MVP

0.12

MPC

0.053

ClinPred

0.0037

GERP RS

3.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.060

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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