Genetic Variant NM_006556.4:c.*48_*49insGGGGGGGGGGGG (chr1-154925080-G-GCCCCCCCCCCCC) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS2_Supporting

The NM_006556.4(PMVK):c.*48_*49insGGGGGGGGGGGG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000381 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: 0.0000038 ( 0 hom. )

Consequence

PMVK
NM_006556.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00600

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS2

High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PMVK	NM_006556.4 link	c.48_49insGGGGGGGGGGGG	3_prime_UTR_variant	Exon 5 of 5	ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3 link	c.48_49insGGGGGGGGGGGG	3_prime_UTR_variant	Exon 5 of 5		NP_001309940.1
PMVK	NM_001323012.3 link	c.48_49insGGGGGGGGGGGG	3_prime_UTR_variant	Exon 5 of 5		NP_001309941.1
PMVK	NM_001348696.2 link	c.48_49insGGGGGGGGGGGG	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 link	c.48_49insGGGGGGGGGGGG		3_prime_UTR_variant	Exon 5 of 5	1	NM_006556.4	ENSP00000357452.3		Q15126

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000834

AC:

AN:

239750

Hom.:

AF XY:

0.00000771

AC XY:

AN XY:

129766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000910

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000381

AC:

AN:

1313216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

651352

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000244

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000321

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000446

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000193

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

NM_006556.4:c.48_49insGGGGGGGGGGGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over