1-154925080-GCC-GCCCCCCCC

Variant names:

• chr1-154925080-G-GCCCCCC
• rs112859764
• NM_006556.4:c.*48_*49insGGGGGG

Variant summary

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

The NM_006556.4(PMVK):​c.*48_*49insGGGGGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,313,114 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.00019 (1 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 251 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 145954 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000338 AC: 81 AN: 239750 Hom.: 0 AF XY: 0.000301 AC XY: 39 AN XY: 129766

Gnomad AFR exome AF: 0.000320

Gnomad AMR exome AF: 0.000823

Gnomad ASJ exome AF: 0.000314

Gnomad EAS exome AF: 0.000515

Gnomad SAS exome AF: 0.000137

Gnomad FIN exome AF: 0.000207

Gnomad NFE exome AF: 0.000227

Gnomad OTH exome AF: 0.000689

GnomAD4 exome AF: 0.000191 AC: 251 AN: 1313114 Hom.: 1 Cov.: 22 AF XY: 0.000192 AC XY: 125 AN XY: 651298

Gnomad4 AFR exome AF: 0.000326

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.000420

Gnomad4 EAS exome AF: 0.000193

Gnomad4 SAS exome AF: 0.000520

Gnomad4 FIN exome AF: 0.000201

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.000289

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000685 AC: 1 AN: 145954 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 70732

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: 0.0000149

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;