NM_006556.4:c.312+234_312+249delATTTATTTATTTATTT

Variant names:

• chr1-154928774-AAAATAAATAAATAAAT-A
• rs55948301
• NM_006556.4:c.312+234_312+249delATTTATTTATTTATTT

Variant summary

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

The NM_006556.4(PMVK):​c.312+234_312+249delATTTATTTATTTATTT 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 0.00013 (0 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: 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+234_312+249delATTTATTTATTTATTT		intron	N/A	NP_006547.1	Q6FGV9
	PMVK	NM_001323011.3		c.270+234_270+249delATTTATTTATTTATTT		intron	N/A	NP_001309940.1
	PMVK	NM_001323012.3		c.87+234_87+249delATTTATTTATTTATTT		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+234_312+249delATTTATTTATTTATTT		intron	N/A	ENSP00000357452.3	Q15126
	PMVK	ENST00000940351.1		c.504+234_504+249delATTTATTTATTTATTT		intron	N/A	ENSP00000610410.1
	PMVK	ENST00000885059.1		c.351+234_351+249delATTTATTTATTTATTT		intron	N/A	ENSP00000555118.1

Frequencies

GnomAD3 genomes AF: 0.000127 AC: 18 AN: 142024 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000697

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00265

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000608

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000127 AC: 18 AN: 142082 Hom.: 0 Cov.: 0 AF XY: 0.000189 AC XY: 13 AN XY: 68690

African (AFR) AF: 0.0000267 AC: 1 AN: 37388

American (AMR) AF: 0.0000696 AC: 1 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

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

South Asian (SAS) AF: 0.00266 AC: 12 AN: 4510

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

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

European-Non Finnish (NFE) AF: 0.0000608 AC: 4 AN: 65750

Other (OTH) AF: 0.00 AC: 0 AN: 1942

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000831

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;