1-154925080-GCC-GCCCCCCC

Variant names:

• chr1-154925080-G-GCCCCC
• rs112859764
• NM_006556.4:c.*48_*49insGGGGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006556.4(PMVK):​c.*48_*49insGGGGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,313,170 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: 𝑓 0.0000069 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000037 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMVK	NM_006556.4	c.*48_*49insGGGGG		3_prime_UTR_variant	Exon 5 of 5	ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.*48_*49insGGGGG		3_prime_UTR_variant	Exon 5 of 5		NP_001309940.1
PMVK	NM_001323012.3	c.*48_*49insGGGGG		3_prime_UTR_variant	Exon 5 of 5		NP_001309941.1
PMVK	NM_001348696.2	c.*48_*49insGGGGG		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	ENST00000368467.4	c.*48_*49insGGGGG		3_prime_UTR_variant	Exon 5 of 5	1	NM_006556.4	ENSP00000357452.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 145974 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000626 AC: 15 AN: 239750 Hom.: 0 AF XY: 0.0000462 AC XY: 6 AN XY: 129766

Gnomad AFR exome AF: 0.0000641

Gnomad AMR exome AF: 0.000183

Gnomad ASJ exome AF: 0.000210

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000683

Gnomad FIN exome AF: 0.000104

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000373 AC: 49 AN: 1313170 Hom.: 0 Cov.: 22 AF XY: 0.0000368 AC XY: 24 AN XY: 651330

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000366

Gnomad4 ASJ exome AF: 0.000186

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000866

Gnomad4 FIN exome AF: 0.0000446

Gnomad4 NFE exome AF: 0.0000168

Gnomad4 OTH exome AF: 0.0000771

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000685 AC: 1 AN: 145974 Hom.: 0 Cov.: 26 AF XY: 0.0000141 AC XY: 1 AN XY: 70744

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

LitVar

Other links and lift over

dbSNP: rs112859764; hg19: chr1-154897556;