19-43507763-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000600651.5(ETHE1):c.*110A>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 0.14 ( 903 hom., cov: 7)
Exomes 𝑓: 0.15 ( 4383 hom. )
Consequence
ETHE1
ENST00000600651.5 3_prime_UTR
ENST00000600651.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.118
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 19-43507763-T-C is Benign according to our data. Variant chr19-43507763-T-C is described in ClinVar as [Benign]. Clinvar id is 671647.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETHE1 | NM_014297.5 | c.712+181A>G | intron_variant | ENST00000292147.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETHE1 | ENST00000600651.5 | c.*110A>G | 3_prime_UTR_variant | 6/6 | 1 | ||||
ETHE1 | ENST00000292147.7 | c.712+181A>G | intron_variant | 1 | NM_014297.5 | P1 | |||
ETHE1 | ENST00000594342.5 | c.*275+181A>G | intron_variant, NMD_transcript_variant | 2 | |||||
ETHE1 | ENST00000598330.1 | c.*456A>G | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.142 AC: 7279AN: 51350Hom.: 902 Cov.: 7
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GnomAD4 exome AF: 0.145 AC: 36073AN: 248696Hom.: 4383 Cov.: 4 AF XY: 0.142 AC XY: 19318AN XY: 136020
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Ethylmalonic encephalopathy Benign:1
Benign, reviewed by expert panel | curation | ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen | May 07, 2021 | The allele frequency of the c.712+181A>G variant in the ETHE1 gene is reported as >12% in gnomAD, including 167 homozygotes, which is high enough to be classified as benign based on thresholds defined by the ClinGen ETHE1 Variant Curation Expert Panel (>0.1% in gnomAD- BA1 and BS2). In silico splicing predictors (Splice AI) for this intronic variant do not predict a deleterious effect (BP7). In summary, this variant meets criteria to be classified as benign for ETHE1-related ethylmalonic encephalopathy. ETHE1-specific ACMG/AMP criteria applied: (BA1, BS2, BP7). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at