rs1555765701
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_014297.5(ETHE1):c.34C>T(p.Gln12Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q12Q) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ETHE1
NM_014297.5 stop_gained
NM_014297.5 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 2.29
Genes affected
ETHE1 (HGNC:23287): (ETHE1 persulfide dioxygenase) This gene encodes a member of the metallo beta-lactamase family of iron-containing proteins involved in the mitochondrial sulfide oxidation pathway. The encoded protein catalyzes the oxidation of a persulfide substrate to sulfite. Certain mutations in this gene cause ethylmalonic encephalopathy, an infantile metabolic disorder affecting the brain, gastrointestinal tract and peripheral vessels. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
ZNF575 (HGNC:27606): (zinc finger protein 575) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 36 pathogenic variants in the truncated region.
PP5
?
Variant 19-43527144-G-A is Pathogenic according to our data. Variant chr19-43527144-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 504490.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETHE1 | NM_014297.5 | c.34C>T | p.Gln12Ter | stop_gained | 1/7 | ENST00000292147.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETHE1 | ENST00000292147.7 | c.34C>T | p.Gln12Ter | stop_gained | 1/7 | 1 | NM_014297.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1396248Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 689910
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1396248
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
689910
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ethylmalonic encephalopathy Pathogenic:1Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2023 | This sequence change creates a premature translational stop signal (p.Gln12*) in the ETHE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ETHE1 are known to be pathogenic (PMID: 14732903, 19136963). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ethylmalonic encephalopathy (PMID: 16183799). ClinVar contains an entry for this variant (Variation ID: 504490). For these reasons, this variant has been classified as Pathogenic. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
MutationTaster
Benign
D;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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