chr1-154926417-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_006556.4(PMVK):​c.379C>T​(p.Gln127Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

PMVK
NM_006556.4 stop_gained

Scores

2
4
1

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.00
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.345 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-154926417-G-A is Pathogenic according to our data. Variant chr1-154926417-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1344671.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PMVKNM_006556.4 linkuse as main transcriptc.379C>T p.Gln127Ter stop_gained 4/5 ENST00000368467.4
PMVKNM_001323011.3 linkuse as main transcriptc.337C>T p.Gln113Ter stop_gained 4/5
PMVKNM_001323012.3 linkuse as main transcriptc.154C>T p.Gln52Ter stop_gained 4/5
PMVKNM_001348696.2 linkuse as main transcriptc.154C>T p.Gln52Ter stop_gained 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PMVKENST00000368467.4 linkuse as main transcriptc.379C>T p.Gln127Ter stop_gained 4/51 NM_006556.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Linear porokeratosis Pathogenic:1
Likely pathogenic, no assertion criteria providedliterature onlyYale Center for Mendelian Genomics, Yale UniversityMay 01, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.60
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
36
DANN
Uncertain
0.99
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.86
D
MutationTaster
Benign
1.0
A
Vest4
0.28
GERP RS
3.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154898893; API