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. Variant got -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

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 1473 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMVK	NM_006556.4	c.312+242_312+249delATTTATTT		intron_variant	Intron 3 of 4	ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.270+242_270+249delATTTATTT		intron_variant	Intron 3 of 4		NP_001309940.1
PMVK	NM_001323012.3	c.87+242_87+249delATTTATTT		intron_variant	Intron 3 of 4		NP_001309941.1
PMVK	NM_001348696.2	c.87+242_87+249delATTTATTT		intron_variant	Intron 3 of 4		NP_001335625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMVK	ENST00000368467.4	c.312+242_312+249delATTTATTT		intron_variant	Intron 3 of 4	1	NM_006556.4	ENSP00000357452.3

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

Gnomad4 AFR AF: 0.00546

Gnomad4 AMR AF: 0.00870

Gnomad4 ASJ AF: 0.00293

Gnomad4 EAS AF: 0.00164

Gnomad4 SAS AF: 0.00155

Gnomad4 FIN AF: 0.00554

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.00772

Bravo AF: 0.0104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55948301; hg19: chr1-154901250;