chr1-154928774-A-AAAAT

Position:

• chr1-154928774-A-AAAAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006556.4(PMVK):​c.312+249_312+250insATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (7675 hom., cov: 0)
• Consequence: PMVK NM_006556.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.584

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 -10 ACMG points.

• BP6: Variant 1-154928774-A-AAAAT is Benign according to our data. Variant chr1-154928774-A-AAAAT is described in ClinVar as [Benign]. Clinvar id is 1257436.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMVK	NM_006556.4	c.312+249_312+250insATTT		intron_variant		ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.270+249_270+250insATTT		intron_variant			NP_001309940.1
PMVK	NM_001323012.3	c.87+249_87+250insATTT		intron_variant			NP_001309941.1
PMVK	NM_001348696.2	c.87+249_87+250insATTT		intron_variant			NP_001335625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMVK	ENST00000368467.4	c.312+249_312+250insATTT		intron_variant		1	NM_006556.4	ENSP00000357452	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 45884 AN: 141762 Hom.: 7669 Cov.: 0

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.324 AC: 45914 AN: 141816 Hom.: 7675 Cov.: 0 AF XY: 0.325 AC XY: 22273 AN XY: 68544

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.306

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

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;