rs121918326
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The ENST00000367999.9(PPOX):c.59A>C(p.His20Pro) variant causes a missense change. 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
PPOX
ENST00000367999.9 missense
ENST00000367999.9 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 6.13
Genes affected
PPOX (HGNC:9280): (protoporphyrinogen oxidase) This gene encodes the penultimate enzyme of heme biosynthesis, which catalyzes the 6-electron oxidation of protoporphyrinogen IX to form protoporphyrin IX. Mutations in this gene cause variegate porphyria, an autosomal dominant disorder of heme metabolism resulting from a deficiency in protoporphyrinogen oxidase, an enzyme located on the inner mitochondrial membrane. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.982
PP5
Variant 1-161166906-A-C is Pathogenic according to our data. Variant chr1-161166906-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 8695.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPOX | NM_001122764.3 | c.59A>C | p.His20Pro | missense_variant | 2/13 | ENST00000367999.9 | NP_001116236.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPOX | ENST00000367999.9 | c.59A>C | p.His20Pro | missense_variant | 2/13 | 1 | NM_001122764.3 | ENSP00000356978 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Variegate porphyria Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1996 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;.;D;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.;.;.;.
MutationTaster
Benign
A;A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;N;N;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.;T;D;.
Sift4G
Uncertain
D;D;.;D;D;.
Polyphen
P;P;.;P;.;.
Vest4
MutPred
Gain of glycosylation at H20 (P = 0.0227);Gain of glycosylation at H20 (P = 0.0227);Gain of glycosylation at H20 (P = 0.0227);Gain of glycosylation at H20 (P = 0.0227);Gain of glycosylation at H20 (P = 0.0227);Gain of glycosylation at H20 (P = 0.0227);
MVP
MPC
1.5
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