19-43526205-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_014297.5(ETHE1):c.371G>T(p.Arg124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★★). Synonymous variant affecting the same amino acid position (i.e. R124R) has been classified as Likely benign.
Frequency
Consequence
NM_014297.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETHE1 | NM_014297.5 | c.371G>T | p.Arg124Leu | missense_variant | 3/7 | ENST00000292147.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETHE1 | ENST00000292147.7 | c.371G>T | p.Arg124Leu | missense_variant | 3/7 | 1 | NM_014297.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251406Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135886
GnomAD4 exome AF: 0.0000705 AC: 103AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727232
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
Ethylmalonic encephalopathy Uncertain:2
Uncertain significance, reviewed by expert panel | curation | ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen | Aug 18, 2020 | This variant was classified as a variant of uncertain significance as there has not been sufficient evidence to support either a benign or a pathogenic classification. Specifically, this variant has not been reported in the literature in affected or unaffected patients, has no published functional data, and although present in population databases with an allele frequency of 0.009%, it does not meet any of the cutoffs supporting a pathogenic or benign classification. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 14, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at