chr1-154939322-A-G

Position:

• chr1-154939322-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001323012.3(PMVK):​c.-131+3254T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,944 control chromosomes in the GnomAD database, including 10,945 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (10945 hom., cov: 31)
• Consequence: PMVK NM_001323012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMVK	NM_001323012.3	c.-131+3254T>C		intron_variant			NP_001309941.1
		n.154939322A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49760 AN: 151826 Hom.: 10948 Cov.: 31

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.327 AC: 49754 AN: 151944 Hom.: 10945 Cov.: 31 AF XY: 0.338 AC XY: 25109 AN XY: 74252

Gnomad4 AFR AF: 0.0766

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.355

Alfa AF: 0.329 Hom.: 2345

Bravo AF: 0.327

Asia WGS AF: 0.652 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.4
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4845695; hg19: chr1-154911798;