chr1-154928774-A-AAAATAAATAAAT

Variant names:

• chr1-154928774-A-AAAATAAATAAAT
• rs55948301
• NM_006556.4:c.312+238_312+249dupATTTATTTATTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006556.4(PMVK):​c.312+238_312+249dupATTTATTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0027 (0 hom., cov: 0)
• Consequence: PMVK NM_006556.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• 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: Uncertain_significance. The variant received 0 ACMG points.

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+238_312+249dupATTTATTTATTT		intron	N/A	NP_006547.1	Q6FGV9
	PMVK	NM_001323011.3		c.270+238_270+249dupATTTATTTATTT		intron	N/A	NP_001309940.1
	PMVK	NM_001323012.3		c.87+238_87+249dupATTTATTTATTT		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+249_312+250insATTTATTTATTT		intron	N/A	ENSP00000357452.3	Q15126
	PMVK	ENST00000940351.1		c.504+249_504+250insATTTATTTATTT		intron	N/A	ENSP00000610410.1
	PMVK	ENST00000885059.1		c.351+249_351+250insATTTATTTATTT		intron	N/A	ENSP00000555118.1

Frequencies

GnomAD3 genomes AF: 0.00270 AC: 384 AN: 142016 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00708

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000442

Gnomad FIN AF: 0.00346

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000989

Gnomad OTH AF: 0.00260

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

GnomAD4 genome AF: 0.00270 AC: 384 AN: 142074 Hom.: 0 Cov.: 0 AF XY: 0.00258 AC XY: 177 AN XY: 68686

African (AFR) AF: 0.00706 AC: 264 AN: 37384

American (AMR) AF: 0.00118 AC: 17 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 4880

South Asian (SAS) AF: 0.000443 AC: 2 AN: 4510

European-Finnish (FIN) AF: 0.00346 AC: 30 AN: 8664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000989 AC: 65 AN: 65746

Other (OTH) AF: 0.00257 AC: 5 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		0.58
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;