1-154932703-A-G

Position:

• chr1-154932703-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006556.4(PMVK):​c.96-288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,224 control chromosomes in the GnomAD database, including 7,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (7363 hom., cov: 32)
• Consequence: PMVK NM_006556.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.261

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-154932703-A-G is Benign according to our data. Variant chr1-154932703-A-G is described in ClinVar as [Benign]. Clinvar id is 1227224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMVK	NM_006556.4	c.96-288T>C		intron_variant		ENST00000368467.4	NP_006547.1
PMVK	NM_001323011.3	c.54-288T>C		intron_variant			NP_001309940.1
PMVK	NM_001323012.3	c.-130-288T>C		intron_variant			NP_001309941.1
PMVK	NM_001348696.2	c.-11-288T>C		intron_variant			NP_001335625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMVK	ENST00000368467.4	c.96-288T>C		intron_variant		1	NM_006556.4	ENSP00000357452	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31424 AN: 152106 Hom.: 7320 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.207 AC: 31520 AN: 152224 Hom.: 7363 Cov.: 32 AF XY: 0.201 AC XY: 14950 AN XY: 74424

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.0668

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0608

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.158

Alfa AF: 0.0518 Hom.: 118

Bravo AF: 0.225

Asia WGS AF: 0.0930 AC: 323 AN: 3478

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.67

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: rs7543051; hg19: chr1-154905179;