Genetic Variant PMVK:c.312+246_312+249dupATTT (chr1-154928774-A-AAAAT) – 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+246_312+249dupATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 7675 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-AAAAT is Benign according to our data. Variant chr1-154928774-A-AAAAT is described in ClinVar as Benign. ClinVar VariationId is 1257436.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 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+246_312+249dupATTT	intron	N/A	NP_006547.1	Q6FGV9
PMVK	NM_001323011.3		c.270+246_270+249dupATTT	intron	N/A	NP_001309940.1
PMVK	NM_001323012.3		c.87+246_87+249dupATTT	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+250insATTT	intron	N/A	ENSP00000357452.3	Q15126
PMVK	ENST00000940351.1		c.504+249_504+250insATTT	intron	N/A	ENSP00000610410.1
PMVK	ENST00000885059.1		c.351+249_351+250insATTT	intron	N/A	ENSP00000555118.1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

45884

AN:

141762

Hom.:

7669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.301

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

GnomAD4 genome

AF:

0.324

AC:

45914

AN:

141816

Hom.:

7675

Cov.:

AF XY:

0.325

AC XY:

22273

AN XY:

68544

show subpopulations

African (AFR)

AF:

0.372

AC:

13881

AN:

37286

American (AMR)

AF:

0.254

AC:

3635

AN:

14334

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

670

AN:

3410

East Asian (EAS)

AF:

0.297

AC:

1448

AN:

4876

South Asian (SAS)

AF:

0.255

AC:

1146

AN:

4502

European-Finnish (FIN)

AF:

0.341

AC:

2944

AN:

8630

Middle Eastern (MID)

AF:

0.248

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.324

AC:

21257

AN:

65664

Other (OTH)

AF:

0.306

AC:

595

AN:

1942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1421

2842

4262

5683

7104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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