1-154928774-AAAATAAATAAATAAATAAAT-AAAATAAATAAATAAAT

Variant names:

• chr1-154928774-AAAAT-A
• rs55948301
• NM_006556.4:c.312+246_312+249delATTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006556.4(PMVK):​c.312+246_312+249delATTT 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 0.018 (43 hom., cov: 0)
• Consequence: PMVK NM_006556.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 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.312+246_312+249delATTT		intron	N/A	NP_006547.1	Q6FGV9
	PMVK	NM_001323011.3		c.270+246_270+249delATTT		intron	N/A	NP_001309940.1
	PMVK	NM_001323012.3		c.87+246_87+249delATTT		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+246_312+249delATTT		intron	N/A	ENSP00000357452.3	Q15126
	PMVK	ENST00000940351.1		c.504+246_504+249delATTT		intron	N/A	ENSP00000610410.1
	PMVK	ENST00000885059.1		c.351+246_351+249delATTT		intron	N/A	ENSP00000555118.1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2490 AN: 142002 Hom.: 43 Cov.: 0

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00990

Gnomad ASJ AF: 0.00996

Gnomad EAS AF: 0.00266

Gnomad SAS AF: 0.00133

Gnomad FIN AF: 0.00115

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.00309

Gnomad OTH AF: 0.0166

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

GnomAD4 genome AF: 0.0176 AC: 2499 AN: 142060 Hom.: 43 Cov.: 0 AF XY: 0.0166 AC XY: 1141 AN XY: 68684

African (AFR) AF: 0.0550 AC: 2056 AN: 37368

American (AMR) AF: 0.00989 AC: 142 AN: 14360

Ashkenazi Jewish (ASJ) AF: 0.00996 AC: 34 AN: 3412

East Asian (EAS) AF: 0.00266 AC: 13 AN: 4880

South Asian (SAS) AF: 0.00133 AC: 6 AN: 4510

European-Finnish (FIN) AF: 0.00115 AC: 10 AN: 8664

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

European-Non Finnish (NFE) AF: 0.00309 AC: 203 AN: 65750

Other (OTH) AF: 0.0165 AC: 32 AN: 1942

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism

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: rs55948301; hg19: chr1-154901250;