1-154928774-AAAATAAATAAATAAATAAAT-AAAATAAAT

Variant names:

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

Variant summary

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

The NM_006556.4(PMVK):​c.312+238_312+249delATTTATTTATTT 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 DEL_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 0.0031 (5 hom., cov: 0)
• Consequence: PMVK NM_006556.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.907
• 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 5 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+238_312+249delATTTATTTATTT		intron	N/A	NP_006547.1	Q6FGV9
	PMVK	NM_001323011.3		c.270+238_270+249delATTTATTTATTT		intron	N/A	NP_001309940.1
	PMVK	NM_001323012.3		c.87+238_87+249delATTTATTTATTT		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+238_312+249delATTTATTTATTT		intron	N/A	ENSP00000357452.3	Q15126
	PMVK	ENST00000940351.1		c.504+238_504+249delATTTATTTATTT		intron	N/A	ENSP00000610410.1
	PMVK	ENST00000885059.1		c.351+238_351+249delATTTATTTATTT		intron	N/A	ENSP00000555118.1

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 438 AN: 142020 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00718

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00160

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.00531

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.000791

Gnomad OTH AF: 0.00468

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

GnomAD4 genome AF: 0.00309 AC: 439 AN: 142078 Hom.: 5 Cov.: 0 AF XY: 0.00309 AC XY: 212 AN XY: 68688

African (AFR) AF: 0.00725 AC: 271 AN: 37384

American (AMR) AF: 0.00160 AC: 23 AN: 14362

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

East Asian (EAS) AF: 0.0123 AC: 60 AN: 4880

South Asian (SAS) AF: 0.00488 AC: 22 AN: 4510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8664

Middle Eastern (MID) AF: 0.00352 AC: 1 AN: 284

European-Non Finnish (NFE) AF: 0.000791 AC: 52 AN: 65750

Other (OTH) AF: 0.00463 AC: 9 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		0.91

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;