16-88653337-G-A

Variant names:

• chr16-88653337-G-A
• rs201844867
• NM_002461.3:c.1085C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002461.3(MVD):​c.1085C>T​(p.Pro362Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,600,368 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: MVD NM_002461.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.37
• Publications: 3 publications found

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, G2P, Labcorp Genetics (formerly Invitae)
• disseminated superficial actinic porokeratosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069036186).
• BS2: High AC in GnomAd4 at 20 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002461.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVD	NM_002461.3	MANE Select	c.1085C>T	p.Pro362Leu	missense	Exon 9 of 10	NP_002452.1	P53602

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVD	ENST00000301012.8	TSL:1 MANE Select	c.1085C>T	p.Pro362Leu	missense	Exon 9 of 10	ENSP00000301012.3	P53602
	MVD	ENST00000565149.5	TSL:1	n.1644C>T		non_coding_transcript_exon	Exon 5 of 6
	MVD	ENST00000899622.1		c.1205C>T	p.Pro402Leu	missense	Exon 10 of 11	ENSP00000569681.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152192 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000290 AC: 68 AN: 234806 AF XY: 0.000335

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00602

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000836

Gnomad OTH exome AF: 0.000353

GnomAD4 exome AF: 0.000159 AC: 230 AN: 1448176 Hom.: 2 Cov.: 32 AF XY: 0.000190 AC XY: 137 AN XY: 720748

African (AFR) AF: 0.0000618 AC: 2 AN: 32350

American (AMR) AF: 0.0000750 AC: 3 AN: 40024

Ashkenazi Jewish (ASJ) AF: 0.00614 AC: 157 AN: 25556

East Asian (EAS) AF: 0.00 AC: 0 AN: 39450

South Asian (SAS) AF: 0.0000237 AC: 2 AN: 84524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000361 AC: 40 AN: 1108522

Other (OTH) AF: 0.000435 AC: 26 AN: 59836

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152192 Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000510 Hom.: 0

Bravo AF: 0.000185

ExAC AF: 0.000223 AC: 27

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Benign	0.72
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.10
Sift	Benign	0.65	T
Sift4G	Benign	0.47	T
Polyphen		0.066	B
Vest4		0.38
MVP		0.17
MPC		0.057
ClinPred		0.089	T
GERP RS		3.2
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.28
gMVP		0.59
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs201844867; hg19: chr16-88719745; COSMIC: COSV55368399; COSMIC: COSV55368399;