Variant chr1-154929049-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006556.4(PMVK):c.287T>C(p.Val96Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00596 in 1,614,132 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 32 hom. )

Consequence

PMVK
NM_006556.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.99

Variant links:

Genes affected

PMVK (HGNC:9141): (phosphomevalonate kinase) This gene encodes a peroxisomal enzyme that is a member of the galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase (GHMP) family of ATP-dependent enzymes. The encoded protein catalyzes the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate, which is the fifth step in the mevalonate pathway of isoprenoid biosynthesis. Mutations in this gene are linked to certain types of porokeratosis including disseminated superficial porokeratosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

PMVK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008589804).

BP6

Variant 1-154929049-A-G is Benign according to our data. Variant chr1-154929049-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 377095.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 664 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PMVK	NM_006556.4 linkuse as main transcript	c.287T>C	p.Val96Ala	missense_variant	3/5	ENST00000368467.4
PMVK	NM_001323011.3 linkuse as main transcript	c.245T>C	p.Val82Ala	missense_variant	3/5
PMVK	NM_001323012.3 linkuse as main transcript	c.62T>C	p.Val21Ala	missense_variant	3/5
PMVK	NM_001348696.2 linkuse as main transcript	c.62T>C	p.Val21Ala	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMVK	ENST00000368467.4 linkuse as main transcript	c.287T>C	p.Val96Ala	missense_variant	3/5	1	NM_006556.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00436

AC:

664

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00748

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00431

AC:

1083

AN:

251470

Hom.:

AF XY:

0.00433

AC XY:

589

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.00249

Gnomad NFE exome

AF:

0.00784

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00612

AC:

8953

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

4398

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00141

Gnomad4 FIN exome

AF:

0.00296

Gnomad4 NFE exome

AF:

0.00739

Gnomad4 OTH exome

AF:

0.00558

GnomAD4 genome

AF:

0.00436

AC:

664

AN:

152288

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00747

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00640

Hom.:

Bravo

AF:

0.00454

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00518

AC:

629

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PMVK-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Nov 07, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

Eigen

Benign

0.083

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.70

M_CAP

Benign

0.011

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.1

REVEL

Benign

0.18

Sift

Benign

0.17

Sift4G

Benign

0.22

Polyphen

0.67

Vest4

0.61

MVP

0.39

MPC

0.92

ClinPred

0.025

GERP RS

5.9

Varity_R

0.41

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over