chr1-154928774-A-AAAATAAAT

Position:

• chr1-154928774-A-AAAATAAAT

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+250insATTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1469 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-AAAATAAAT is Benign according to our data. Variant chr1-154928774-A-AAAATAAAT is described in ClinVar as [Benign]. Clinvar id is 1270881.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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+250insATTTATTT		intron_variant		ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.270+249_270+250insATTTATTT		intron_variant			NP_001309940.1
PMVK	NM_001323012.3	c.87+249_87+250insATTTATTT		intron_variant			NP_001309941.1
PMVK	NM_001348696.2	c.87+249_87+250insATTTATTT		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+250insATTTATTT		intron_variant		1	NM_006556.4	ENSP00000357452	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 14944 AN: 141872 Hom.: 1467 Cov.: 0

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0282

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0466

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0419

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0848

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

GnomAD4 genome AF: 0.105 AC: 14964 AN: 141930 Hom.: 1469 Cov.: 0 AF XY: 0.102 AC XY: 6983 AN XY: 68608

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0485

Gnomad4 ASJ AF: 0.0466

Gnomad4 EAS AF: 0.0145

Gnomad4 SAS AF: 0.0266

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0536

Gnomad4 OTH AF: 0.0840

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 21, 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;