1-154925080-GCC-GC

Variant names:

• chr1-154925080-GC-G
• rs112859764
• NM_006556.4:c.*48delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006556.4(PMVK):​c.*48delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,459,192 control chromosomes in the GnomAD database, including 263 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (185 hom., cov: 26)
  • Exomes 𝑓: 0.0023 (78 hom.)
• Consequence: PMVK NM_006556.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00600
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• porokeratosis 1, Mibelli type

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• porokeratosis of Mibelli

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autoinflammatory syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-154925080-GC-G is Benign according to our data. Variant chr1-154925080-GC-G is described in ClinVar as Benign. ClinVar VariationId is 1259917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006556.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMVK	NM_006556.4	MANE Select	c.*48delG		3_prime_UTR	Exon 5 of 5	NP_006547.1	Q6FGV9
	PMVK	NM_001323011.3		c.*48delG		3_prime_UTR	Exon 5 of 5	NP_001309940.1
	PMVK	NM_001323012.3		c.*48delG		3_prime_UTR	Exon 5 of 5	NP_001309941.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMVK	ENST00000368467.4	TSL:1 MANE Select	c.*48delG		3_prime_UTR	Exon 5 of 5	ENSP00000357452.3	Q15126
	PMVK	ENST00000940351.1		c.*48delG		3_prime_UTR	Exon 6 of 6	ENSP00000610410.1
	PMVK	ENST00000885059.1		c.*48delG		3_prime_UTR	Exon 6 of 6	ENSP00000555118.1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 3944 AN: 145960 Hom.: 186 Cov.: 26

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0223

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0333

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0212

GnomAD2 exomes AF: 0.00870 AC: 2086 AN: 239750 AF XY: 0.00680

Gnomad AFR exome AF: 0.0942

Gnomad AMR exome AF: 0.00646

Gnomad ASJ exome AF: 0.0200

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00152

Gnomad OTH exome AF: 0.00724

GnomAD4 exome AF: 0.00230 AC: 3022 AN: 1313148 Hom.: 78 Cov.: 22 AF XY: 0.00210 AC XY: 1370 AN XY: 651308

African (AFR) AF: 0.0618 AC: 1704 AN: 27556

American (AMR) AF: 0.00568 AC: 233 AN: 41022

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 313 AN: 21448

East Asian (EAS) AF: 0.00 AC: 0 AN: 31120

South Asian (SAS) AF: 0.000285 AC: 23 AN: 80822

European-Finnish (FIN) AF: 0.0000223 AC: 1 AN: 44866

Middle Eastern (MID) AF: 0.00815 AC: 41 AN: 5030

European-Non Finnish (NFE) AF: 0.000473 AC: 477 AN: 1009376

Other (OTH) AF: 0.00443 AC: 230 AN: 51908

GnomAD4 genome AF: 0.0270 AC: 3946 AN: 146044 Hom.: 185 Cov.: 26 AF XY: 0.0262 AC XY: 1859 AN XY: 70834

African (AFR) AF: 0.0918 AC: 3573 AN: 38912

American (AMR) AF: 0.0121 AC: 171 AN: 14168

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 77 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 4950

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9620

Middle Eastern (MID) AF: 0.0324 AC: 9 AN: 278

European-Non Finnish (NFE) AF: 0.00109 AC: 73 AN: 67090

Other (OTH) AF: 0.0210 AC: 42 AN: 2000

Alfa AF: 0.0193 Hom.: 10

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0060
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs112859764; hg19: chr1-154897556;