Genetic Variant MVD:p.Ala399Gly (chr16-88652532-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002461.3(MVD):c.1196C>G(p.Ala399Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,419,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MVD
NM_002461.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.394

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

porokeratosis 7, multiple types
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
disseminated superficial actinic porokeratosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MVD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07266995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVD	NM_002461.3 link	c.1196C>G	p.Ala399Gly	missense_variant	Exon 10 of 10	ENST00000301012.8	NP_002452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MVD	ENST00000301012.8 link	c.1196C>G	p.Ala399Gly	missense_variant	Exon 10 of 10	1	NM_002461.3	ENSP00000301012.3	P53602
MVD	ENST00000565149.5 link	n.1755C>G		non_coding_transcript_exon_variant	Exon 6 of 6	1
MVD	ENST00000561895.1 link	n.477C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
MVD	ENST00000562981.1 link	n.359C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000540

AC:

AN:

185304

AF XY:

0.0000101

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1419198

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32524

American (AMR)

AF:

0.00

AC:

AN:

39096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25398

East Asian (EAS)

AF:

0.00

AC:

AN:

37422

South Asian (SAS)

AF:

0.0000247

AC:

AN:

80892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090160

Other (OTH)

AF:

0.00

AC:

AN:

58764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000848

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1196C>G (p.A399G) alteration is located in exon 10 (coding exon 10) of the MVD gene. This alteration results from a C to G substitution at nucleotide position 1196, causing the alanine (A) at amino acid position 399 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.6

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.16

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.54

M_CAP

Benign

0.0089

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.39

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.3

REVEL

Benign

0.028

Sift

Benign

0.067

Sift4G

Benign

0.26

Polyphen

0.020

Vest4

0.12

MutPred

0.10

Gain of catalytic residue at A400 (P = 0.0751);

MVP

0.076

MPC

0.053

ClinPred

0.58

GERP RS

-1.6

Varity_R

0.11

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

16-88652532-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over