Variant 1-154932364-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006556.4(PMVK):c.147A>G(p.Glu49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 1,612,024 control chromosomes in the GnomAD database, including 16,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 7368 hom., cov: 32)

Exomes 𝑓: 0.077 ( 9538 hom. )

Consequence

PMVK
NM_006556.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0670

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-154932364-T-C is Benign according to our data. Variant chr1-154932364-T-C is described in ClinVar as [Benign]. Clinvar id is 1278538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.067 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PMVK	NM_006556.4 linkuse as main transcript	c.147A>G	p.Glu49=	synonymous_variant	2/5	ENST00000368467.4
PMVK	NM_001348696.2 linkuse as main transcript	c.41A>G	p.Asn14Ser	missense_variant	2/5
PMVK	NM_001323011.3 linkuse as main transcript	c.105A>G	p.Glu35=	synonymous_variant	2/5
PMVK	NM_001323012.3 linkuse as main transcript	c.-79A>G		5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMVK	ENST00000368467.4 linkuse as main transcript	c.147A>G	p.Glu49=	synonymous_variant	2/5	1	NM_006556.4	P1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31427

AN:

151924

Hom.:

7325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.580

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0977

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0613

Gnomad FIN

AF:

0.0559

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.0656

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.0953

AC:

23888

AN:

250722

Hom.:

3411

AF XY:

0.0861

AC XY:

11671

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.597

Gnomad AMR exome

AF:

0.0573

Gnomad ASJ exome

AF:

0.0643

Gnomad EAS exome

AF:

0.000816

Gnomad SAS exome

AF:

0.0689

Gnomad FIN exome

AF:

0.0583

Gnomad NFE exome

AF:

0.0686

Gnomad OTH exome

AF:

0.0800

GnomAD4 exome

AF:

0.0774

AC:

113004

AN:

1459984

Hom.:

9538

Cov.:

AF XY:

0.0752

AC XY:

54633

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.604

Gnomad4 AMR exome

AF:

0.0618

Gnomad4 ASJ exome

AF:

0.0652

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.0693

Gnomad4 FIN exome

AF:

0.0573

Gnomad4 NFE exome

AF:

0.0655

Gnomad4 OTH exome

AF:

0.0971

GnomAD4 genome

AF:

0.207

AC:

31522

AN:

152040

Hom.:

7368

Cov.:

AF XY:

0.201

AC XY:

14948

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.581

Gnomad4 AMR

AF:

0.0975

Gnomad4 ASJ

AF:

0.0669

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0608

Gnomad4 FIN

AF:

0.0559

Gnomad4 NFE

AF:

0.0656

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.0929

Hom.:

3663

Bravo

AF:

0.225

Asia WGS

AF:

0.0930

AC:

323

AN:

3478

EpiCase

AF:

0.0639

EpiControl

AF:

0.0671

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -

PMVK-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.7

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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