chr1-154925080-G-GCCCCCCCCCCCCCCCCCCCC

Variant names:

• chr1-154925080-G-GCCCCCCCCCCCCCCCCCCCC
• NM_006556.4:c.*48_*49insGGGGGGGGGGGGGGGGGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006556.4(PMVK):​c.*48_*49insGGGGGGGGGGGGGGGGGGGG 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 1,313,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMVK	NM_006556.4	c.*48_*49insGGGGGGGGGGGGGGGGGGGG		3_prime_UTR_variant	Exon 5 of 5	ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.*48_*49insGGGGGGGGGGGGGGGGGGGG		3_prime_UTR_variant	Exon 5 of 5		NP_001309940.1
PMVK	NM_001323012.3	c.*48_*49insGGGGGGGGGGGGGGGGGGGG		3_prime_UTR_variant	Exon 5 of 5		NP_001309941.1
PMVK	NM_001348696.2	c.*48_*49insGGGGGGGGGGGGGGGGGGGG		3_prime_UTR_variant	Exon 5 of 5		NP_001335625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMVK	ENST00000368467	c.*48_*49insGGGGGGGGGGGGGGGGGGGG		3_prime_UTR_variant	Exon 5 of 5	1	NM_006556.4	ENSP00000357452.3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 7.61e-7 AC: 1 AN: 1313216 Hom.: 0 Cov.: 22 AF XY: 0.00000154 AC XY: 1 AN XY: 651352

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.91e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154897556;