Variant 16-88655264-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002461.3(MVD):c.832A>C(p.Asn278His) variant causes a missense change. The variant allele was found at a frequency of 0.00141 in 1,590,402 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0076 ( 13 hom., cov: 34)

Exomes 𝑓: 0.00076 ( 10 hom. )

Consequence

MVD
NM_002461.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.19

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:

MVD (HGNC:):

MVD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052857697).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00755 (1150/152304) while in subpopulation AFR AF= 0.0261 (1085/41562). AF 95% confidence interval is 0.0248. There are 13 homozygotes in gnomad4. There are 553 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVD	NM_002461.3 linkuse as main transcript	c.832A>C	p.Asn278His	missense_variant	7/10	ENST00000301012.8	NP_002452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVD	ENST00000301012.8 linkuse as main transcript	c.832A>C	p.Asn278His	missense_variant	7/10	1	NM_002461.3	ENSP00000301012.3		P53602
MVD	ENST00000565149.5 linkuse as main transcript	n.1391A>C		non_coding_transcript_exon_variant	3/6	1

Frequencies

GnomAD3 genomes

AF:

0.00754

AC:

1148

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00197

AC:

414

AN:

210158

Hom.:

AF XY:

0.00146

AC XY:

165

AN XY:

112918

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.000925

GnomAD4 exome

AF:

0.000765

AC:

1100

AN:

1438098

Hom.:

Cov.:

AF XY:

0.000706

AC XY:

503

AN XY:

712894

show subpopulations

Gnomad4 AFR exome

AF:

0.0268

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000727

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000382

Gnomad4 OTH exome

AF:

0.00148

GnomAD4 genome

AF:

0.00755

AC:

1150

AN:

152304

Hom.:

Cov.:

AF XY:

0.00742

AC XY:

553

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.00902

ESP6500AA

AF:

0.0290

AC:

127

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00234

AC:

282

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.3

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.22

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.95

Vest4

0.53

MVP

0.22

MPC

0.32

ClinPred

0.13

GERP RS

4.3

Varity_R

0.60

gMVP

0.89

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over