Genetic Variant PMVK:c.312+242_312+249dupATTTATTT (chr1-154928774-A-AAAATAAAT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006556.4(PMVK):c.312+242_312+249dupATTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1469 hom., cov: 0)

Consequence

PMVK
NM_006556.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.584

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

porokeratosis 1, Mibelli type
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
porokeratosis of Mibelli
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autoinflammatory syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

PMVK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-154928774-A-AAAATAAAT is Benign according to our data. Variant chr1-154928774-A-AAAATAAAT is described in ClinVar as Benign. ClinVar VariationId is 1270881.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006556.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PMVK	NM_006556.4	MANE Select	c.312+242_312+249dupATTTATTT	intron	N/A	NP_006547.1	Q6FGV9
PMVK	NM_001323011.3		c.270+242_270+249dupATTTATTT	intron	N/A	NP_001309940.1
PMVK	NM_001323012.3		c.87+242_87+249dupATTTATTT	intron	N/A	NP_001309941.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PMVK	ENST00000368467.4	TSL:1 MANE Select	c.312+249_312+250insATTTATTT	intron	N/A	ENSP00000357452.3	Q15126
PMVK	ENST00000940351.1		c.504+249_504+250insATTTATTT	intron	N/A	ENSP00000610410.1
PMVK	ENST00000885059.1		c.351+249_351+250insATTTATTT	intron	N/A	ENSP00000555118.1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

14944

AN:

141872

Hom.:

1467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.0282

Gnomad AMR

AF:

0.0486

Gnomad ASJ

AF:

0.0466

Gnomad EAS

AF:

0.0147

Gnomad SAS

AF:

0.0277

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.0419

Gnomad NFE

AF:

0.0536

Gnomad OTH

AF:

0.0848

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.105

AC:

14964

AN:

141930

Hom.:

1469

Cov.:

AF XY:

0.102

AC XY:

6983

AN XY:

68608

show subpopulations

African (AFR)

AF:

0.267

AC:

9941

AN:

37294

American (AMR)

AF:

0.0485

AC:

696

AN:

14352

Ashkenazi Jewish (ASJ)

AF:

0.0466

AC:

159

AN:

3410

East Asian (EAS)

AF:

0.0145

AC:

AN:

4880

South Asian (SAS)

AF:

0.0266

AC:

120

AN:

4506

European-Finnish (FIN)

AF:

0.0298

AC:

258

AN:

8664

Middle Eastern (MID)

AF:

0.0423

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0536

AC:

3519

AN:

65712

Other (OTH)

AF:

0.0840

AC:

163

AN:

1940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

553

1106

1659

2212

2765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.58

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over