1-154928774-AAAATAAATAAATAAATAAAT-AAAATAAATAAAT

Variant names:

• chr1-154928774-AAAATAAAT-A
• rs55948301
• NM_006556.4:c.312+242_312+249delATTTATTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006556.4(PMVK):​c.312+242_312+249delATTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.010 (9 hom., cov: 0)
• Consequence: PMVK NM_006556.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 9 AD,AR gene

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.312+242_312+249delATTTATTT		intron	N/A	NP_006547.1	Q6FGV9
	PMVK	NM_001323011.3		c.270+242_270+249delATTTATTT		intron	N/A	NP_001309940.1
	PMVK	NM_001323012.3		c.87+242_87+249delATTTATTT		intron	N/A	NP_001309941.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMVK	ENST00000368467.4	TSL:1 MANE Select	c.312+242_312+249delATTTATTT		intron	N/A	ENSP00000357452.3	Q15126
	PMVK	ENST00000940351.1		c.504+242_504+249delATTTATTT		intron	N/A	ENSP00000610410.1
	PMVK	ENST00000885059.1		c.351+242_351+249delATTTATTT		intron	N/A	ENSP00000555118.1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1474 AN: 142012 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.00547

Gnomad AMI AF: 0.0191

Gnomad AMR AF: 0.00872

Gnomad ASJ AF: 0.00293

Gnomad EAS AF: 0.00163

Gnomad SAS AF: 0.00155

Gnomad FIN AF: 0.00554

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.00832

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

GnomAD4 genome AF: 0.0104 AC: 1473 AN: 142070 Hom.: 9 Cov.: 0 AF XY: 0.00922 AC XY: 633 AN XY: 68686

African (AFR) AF: 0.00546 AC: 204 AN: 37384

American (AMR) AF: 0.00870 AC: 125 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.00293 AC: 10 AN: 3412

East Asian (EAS) AF: 0.00164 AC: 8 AN: 4880

South Asian (SAS) AF: 0.00155 AC: 7 AN: 4508

European-Finnish (FIN) AF: 0.00554 AC: 48 AN: 8664

Middle Eastern (MID) AF: 0.0106 AC: 3 AN: 284

European-Non Finnish (NFE) AF: 0.0158 AC: 1036 AN: 65744

Other (OTH) AF: 0.00772 AC: 15 AN: 1942

Alfa AF: 0.00507 Hom.: 0

Bravo AF: 0.0104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs55948301; hg19: chr1-154901250;