Variant 1-154925085-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006556.4(PMVK):c.*44T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 0 hom., cov: 16)

Exomes 𝑓: 0.056 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

PMVK
NM_006556.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.18

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-154925085-A-C is Benign according to our data. Variant chr1-154925085-A-C is described in ClinVar as [Benign]. Clinvar id is 1254973.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PMVK	NM_006556.4 linkuse as main transcript	c.*44T>G	3_prime_UTR_variant	5/5	ENST00000368467.4
PMVK	NM_001323011.3 linkuse as main transcript	c.*44T>G	3_prime_UTR_variant	5/5
PMVK	NM_001323012.3 linkuse as main transcript	c.*44T>G	3_prime_UTR_variant	5/5
PMVK	NM_001348696.2 linkuse as main transcript	c.*44T>G	3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMVK	ENST00000368467.4 linkuse as main transcript	c.*44T>G		3_prime_UTR_variant	5/5	1	NM_006556.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

414

AN:

62072

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.0151

Gnomad AMR

AF:

0.00494

Gnomad ASJ

AF:

0.00526

Gnomad EAS

AF:

0.00785

Gnomad SAS

AF:

0.00511

Gnomad FIN

AF:

0.00334

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00773

Gnomad OTH

AF:

0.00508

GnomAD3 exomes

AF:

0.0632

AC:

12030

AN:

190480

Hom.:

AF XY:

0.0568

AC XY:

5947

AN XY:

104710

show subpopulations

Gnomad AFR exome

AF:

0.0479

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.0980

Gnomad SAS exome

AF:

0.0406

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.0409

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0561

AC:

32805

AN:

584676

Hom.:

Cov.:

AF XY:

0.0562

AC XY:

16554

AN XY:

294534

show subpopulations

Gnomad4 AFR exome

AF:

0.0839

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.0940

Gnomad4 EAS exome

AF:

0.0620

Gnomad4 SAS exome

AF:

0.0951

Gnomad4 FIN exome

AF:

0.0401

Gnomad4 NFE exome

AF:

0.0451

Gnomad4 OTH exome

AF:

0.0650

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00666

AC:

414

AN:

62132

Hom.:

Cov.:

AF XY:

0.00639

AC XY:

190

AN XY:

29714

show subpopulations

Gnomad4 AFR

AF:

0.00609

Gnomad4 AMR

AF:

0.00492

Gnomad4 ASJ

AF:

0.00526

Gnomad4 EAS

AF:

0.00787

Gnomad4 SAS

AF:

0.00511

Gnomad4 FIN

AF:

0.00334

Gnomad4 NFE

AF:

0.00773

Gnomad4 OTH

AF:

0.00500

Alfa

AF:

0.00253

Hom.:

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.24

DANN

Benign

0.46

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