Variant chr1-154926423-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006556.4(PMVK):c.373G>A(p.Val125Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,752 control chromosomes in the GnomAD database, including 1,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.059 ( 891 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 806 hom. )

Consequence

PMVK
NM_006556.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.957

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066597164).

BP6

Variant 1-154926423-C-T is Benign according to our data. Variant chr1-154926423-C-T is described in ClinVar as [Benign]. Clinvar id is 1180221.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PMVK	NM_006556.4 linkuse as main transcript	c.373G>A	p.Val125Met	missense_variant	4/5	ENST00000368467.4
PMVK	NM_001323011.3 linkuse as main transcript	c.331G>A	p.Val111Met	missense_variant	4/5
PMVK	NM_001323012.3 linkuse as main transcript	c.148G>A	p.Val50Met	missense_variant	4/5
PMVK	NM_001348696.2 linkuse as main transcript	c.148G>A	p.Val50Met	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMVK	ENST00000368467.4 linkuse as main transcript	c.373G>A	p.Val125Met	missense_variant	4/5	1	NM_006556.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9032

AN:

152150

Hom.:

890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0251

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0170

AC:

4261

AN:

250886

Hom.:

363

AF XY:

0.0128

AC XY:

1735

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.00712

AC:

10407

AN:

1461484

Hom.:

806

Cov.:

AF XY:

0.00628

AC XY:

4563

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0204

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000979

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0594

AC:

9052

AN:

152268

Hom.:

891

Cov.:

AF XY:

0.0571

AC XY:

4254

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.0250

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0210

Hom.:

257

Bravo

AF:

0.0686

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.195

AC:

857

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.0200

AC:

2432

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.57

DANN

Benign

0.58

DEOGEN2

Benign

0.21

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.83

REVEL

Benign

0.015

Sift

Benign

0.17

Sift4G

Benign

0.11

Polyphen

0.031

Vest4

0.092

MPC

0.43

ClinPred

0.0020

GERP RS

-0.86

Varity_R

0.099

gMVP

0.35

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.

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