1-154926467-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PP3_ModeratePP5BS2_Supporting
The NM_006556.4(PMVK):c.329G>A(p.Arg110Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000322 in 1,613,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 0 hom. )
Consequence
PMVK
NM_006556.4 missense
NM_006556.4 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 5.32
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a mutagenesis_site Approximately 20000-fold decrease in Vmax for MgATP. (size 0) in uniprot entity PMVK_HUMAN
PP3
MetaRNN computational evidence supports a deleterious effect, 0.904
PP5
Variant 1-154926467-C-T is Pathogenic according to our data. Variant chr1-154926467-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1344669.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 28 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMVK | NM_006556.4 | c.329G>A | p.Arg110Gln | missense_variant | 4/5 | ENST00000368467.4 | |
PMVK | NM_001323011.3 | c.287G>A | p.Arg96Gln | missense_variant | 4/5 | ||
PMVK | NM_001323012.3 | c.104G>A | p.Arg35Gln | missense_variant | 4/5 | ||
PMVK | NM_001348696.2 | c.104G>A | p.Arg35Gln | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMVK | ENST00000368467.4 | c.329G>A | p.Arg110Gln | missense_variant | 4/5 | 1 | NM_006556.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152192Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
28
AN:
152192
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000164 AC: 41AN: 250600Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135558
GnomAD3 exomes
AF:
AC:
41
AN:
250600
Hom.:
AF XY:
AC XY:
21
AN XY:
135558
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000337 AC: 492AN: 1461338Hom.: 0 Cov.: 31 AF XY: 0.000314 AC XY: 228AN XY: 726954
GnomAD4 exome
AF:
AC:
492
AN:
1461338
Hom.:
Cov.:
31
AF XY:
AC XY:
228
AN XY:
726954
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000184 AC: 28AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74342
GnomAD4 genome
AF:
AC:
28
AN:
152192
Hom.:
Cov.:
32
AF XY:
AC XY:
13
AN XY:
74342
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
4
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
2
ExAC
AF:
AC:
17
EpiCase
AF:
EpiControl
AF:
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 provided | literature only | Yale Center for Mendelian Genomics, Yale University | May 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at