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. Variant got -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

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMVK	NM_006556.4	c.312+246_312+249delATTT		intron_variant	Intron 3 of 4	ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.270+246_270+249delATTT		intron_variant	Intron 3 of 4		NP_001309940.1
PMVK	NM_001323012.3	c.87+246_87+249delATTT		intron_variant	Intron 3 of 4		NP_001309941.1
PMVK	NM_001348696.2	c.87+246_87+249delATTT		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+246_312+249delATTT		intron_variant	Intron 3 of 4	1	NM_006556.4	ENSP00000357452.3

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

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.00989

Gnomad4 ASJ AF: 0.00996

Gnomad4 EAS AF: 0.00266

Gnomad4 SAS AF: 0.00133

Gnomad4 FIN AF: 0.00115

Gnomad4 NFE AF: 0.00309

Gnomad4 OTH AF: 0.0165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs55948301; hg19: chr1-154901250;