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 Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_006556.4(PMVK):​c.312+234_312+249delATTTATTTATTTATTT 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 0.00013 (0 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 -1 ACMG points.

• BS2: High AC in GnomAd4 at 18 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMVK	NM_006556.4	c.312+234_312+249delATTTATTTATTTATTT		intron_variant	Intron 3 of 4	ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.270+234_270+249delATTTATTTATTTATTT		intron_variant	Intron 3 of 4		NP_001309940.1
PMVK	NM_001323012.3	c.87+234_87+249delATTTATTTATTTATTT		intron_variant	Intron 3 of 4		NP_001309941.1
PMVK	NM_001348696.2	c.87+234_87+249delATTTATTTATTTATTT		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+234_312+249delATTTATTTATTTATTT		intron_variant	Intron 3 of 4	1	NM_006556.4	ENSP00000357452.3

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

Gnomad4 AFR AF: 0.0000267

Gnomad4 AMR AF: 0.0000696

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00266

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000608

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000831

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;