rs34519538

Variant summary

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

The NM_002461.3(MVD):ā€‹c.832A>Cā€‹(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: š‘“ 0.0076 ( 13 hom., cov: 34)
Exomes š‘“: 0.00076 ( 10 hom. )

Consequence

MVD
NM_002461.3 missense

Scores

3
6
9

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]

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
MVDNM_002461.3 linkuse as main transcriptc.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
MVDENST00000301012.8 linkuse as main transcriptc.832A>C p.Asn278His missense_variant 7/101 NM_002461.3 ENSP00000301012.3 P53602
MVDENST00000565149.5 linkuse as main transcriptn.1391A>C non_coding_transcript_exon_variant 3/61

Frequencies

GnomAD3 genomes
AF:
0.00754
AC:
1148
AN:
152186
Hom.:
13
Cov.:
34
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.:
4
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.:
10
Cov.:
32
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.:
13
Cov.:
34
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.:
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34519538; hg19: chr16-88721672; API