rs34519538

Positions:

• chr16-88655264-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.19

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 (HGNC:):

ACMG classification

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	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	c.832A>C	p.Asn278His	missense_variant	7/10	1	NM_002461.3	ENSP00000301012.3
MVD	ENST00000565149.5	n.1391A>C		non_coding_transcript_exon_variant	3/6	1

Frequencies

GnomAD3 genomes AF: 0.00754 AC: 1148 AN: 152186 Hom.: 13 Cov.: 34

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.: 4 AF XY: 0.00146 AC XY: 165 AN XY: 112918

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.: 10 Cov.: 32 AF XY: 0.000706 AC XY: 503 AN XY: 712894

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.: 13 Cov.: 34 AF XY: 0.00742 AC XY: 553 AN XY: 74480

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.: 2

Bravo AF: 0.00902

ESP6500AA AF: 0.0290 AC: 127

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00234 AC: 282

Asia WGS AF: 0.00115 AC: 4 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	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.95	P
Vest4		0.53
MVP		0.22
MPC		0.32
ClinPred		0.13	T
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

Other links and lift over

dbSNP: rs34519538; hg19: chr16-88721672;