1-154925085-A-C

Position:

• chr1-154925085-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_006556.4(PMVK):​c.*44T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (0 hom., cov: 16)
  • Exomes 𝑓: 0.056 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: PMVK NM_006556.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.18

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-154925085-A-C is Benign according to our data. Variant chr1-154925085-A-C is described in ClinVar as [Benign]. Clinvar id is 1254973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMVK	NM_006556.4	c.*44T>G		3_prime_UTR_variant	5/5	ENST00000368467.4
PMVK	NM_001323011.3	c.*44T>G		3_prime_UTR_variant	5/5
PMVK	NM_001323012.3	c.*44T>G		3_prime_UTR_variant	5/5
PMVK	NM_001348696.2	c.*44T>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMVK	ENST00000368467.4	c.*44T>G		3_prime_UTR_variant	5/5	1	NM_006556.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 414 AN: 62072 Hom.: 0 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.00611

Gnomad AMI AF: 0.0151

Gnomad AMR AF: 0.00494

Gnomad ASJ AF: 0.00526

Gnomad EAS AF: 0.00785

Gnomad SAS AF: 0.00511

Gnomad FIN AF: 0.00334

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00773

Gnomad OTH AF: 0.00508

GnomAD3 exomes AF: 0.0632 AC: 12030 AN: 190480 Hom.: 0 AF XY: 0.0568 AC XY: 5947 AN XY: 104710

Gnomad AFR exome AF: 0.0479

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.0980

Gnomad SAS exome AF: 0.0406

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.0409

Gnomad OTH exome AF: 0.107

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0561 AC: 32805 AN: 584676 Hom.: 3 Cov.: 15 AF XY: 0.0562 AC XY: 16554 AN XY: 294534

Gnomad4 AFR exome AF: 0.0839

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.0940

Gnomad4 EAS exome AF: 0.0620

Gnomad4 SAS exome AF: 0.0951

Gnomad4 FIN exome AF: 0.0401

Gnomad4 NFE exome AF: 0.0451

Gnomad4 OTH exome AF: 0.0650

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00666 AC: 414 AN: 62132 Hom.: 0 Cov.: 16 AF XY: 0.00639 AC XY: 190 AN XY: 29714

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.00492

Gnomad4 ASJ AF: 0.00526

Gnomad4 EAS AF: 0.00787

Gnomad4 SAS AF: 0.00511

Gnomad4 FIN AF: 0.00334

Gnomad4 NFE AF: 0.00773

Gnomad4 OTH AF: 0.00500

Alfa AF: 0.00253 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.93
CADD	Benign	0.24
DANN	Benign	0.46

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: rs763078182; hg19: chr1-154897561;