Genetic Variant PMVK:c.*48_*49insGGCGGGGGGGGGGGGGGGGGGGG (chr1-154925080-G-GCCCCCCCCCCCCCCCCCCCCGCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006556.4(PMVK):c.*48_*49insGGCGGGGGGGGGGGGGGGGGGGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,313,220 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

PMVK
NM_006556.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00600

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.48_49insGGCGGGGGGGGGGGGGGGGGGGG	3_prime_UTR	Exon 5 of 5	NP_006547.1	Q6FGV9
PMVK	NM_001323011.3		c.48_49insGGCGGGGGGGGGGGGGGGGGGGG	3_prime_UTR	Exon 5 of 5	NP_001309940.1
PMVK	NM_001323012.3		c.48_49insGGCGGGGGGGGGGGGGGGGGGGG	3_prime_UTR	Exon 5 of 5	NP_001309941.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PMVK	ENST00000368467.4	TSL:1 MANE Select	c.48_49insGGCGGGGGGGGGGGGGGGGGGGG	3_prime_UTR	Exon 5 of 5	ENSP00000357452.3	Q15126
PMVK	ENST00000940351.1		c.48_49insGGCGGGGGGGGGGGGGGGGGGGG	3_prime_UTR	Exon 6 of 6	ENSP00000610410.1
PMVK	ENST00000885059.1		c.48_49insGGCGGGGGGGGGGGGGGGGGGGG	3_prime_UTR	Exon 6 of 6	ENSP00000555118.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.61e-7

AC:

AN:

1313220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

651354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27606

American (AMR)

AF:

0.00

AC:

AN:

41024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21450

East Asian (EAS)

AF:

0.00

AC:

AN:

31120

South Asian (SAS)

AF:

0.00

AC:

AN:

80822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5030

European-Non Finnish (NFE)

AF:

9.91e-7

AC:

AN:

1009388

Other (OTH)

AF:

0.00

AC:

AN:

51912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.0060

Splicing

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

Publications

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1-154925080-GCC-GCCCCCCCCCCCCCCCCCCCCGCCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over