chr1-154928774-AAAATAAATAAAT-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 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

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 439 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMVK	NM_006556.4	c.312+238_312+249delATTTATTTATTT		intron_variant	Intron 3 of 4	ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.270+238_270+249delATTTATTTATTT		intron_variant	Intron 3 of 4		NP_001309940.1
PMVK	NM_001323012.3	c.87+238_87+249delATTTATTTATTT		intron_variant	Intron 3 of 4		NP_001309941.1
PMVK	NM_001348696.2	c.87+238_87+249delATTTATTTATTT		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+238_312+249delATTTATTTATTT		intron_variant	Intron 3 of 4	1	NM_006556.4	ENSP00000357452.3

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

Gnomad4 AFR AF: 0.00725

Gnomad4 AMR AF: 0.00160

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.00488

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000791

Gnomad4 OTH AF: 0.00463

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;