rs116440799
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_014297.5(ETHE1):c.61G>T(p.Ala21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,556,920 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★). Synonymous variant affecting the same amino acid position (i.e. A21A) has been classified as Likely benign.
Frequency
Consequence
NM_014297.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETHE1 | NM_014297.5 | c.61G>T | p.Ala21Ser | missense_variant | 1/7 | ENST00000292147.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETHE1 | ENST00000292147.7 | c.61G>T | p.Ala21Ser | missense_variant | 1/7 | 1 | NM_014297.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0185 AC: 2815AN: 152234Hom.: 70 Cov.: 32
GnomAD3 exomes AF: 0.00478 AC: 741AN: 155116Hom.: 20 AF XY: 0.00394 AC XY: 336AN XY: 85178
GnomAD4 exome AF: 0.00233 AC: 3272AN: 1404570Hom.: 79 Cov.: 32 AF XY: 0.00213 AC XY: 1478AN XY: 694728
GnomAD4 genome ? AF: 0.0185 AC: 2816AN: 152350Hom.: 70 Cov.: 32 AF XY: 0.0177 AC XY: 1322AN XY: 74498
ClinVar
Submissions by phenotype
Ethylmalonic encephalopathy Benign:5
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, reviewed by expert panel | curation | ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen | May 06, 2021 | The allele frequency of the c.61G>T variant in the ETHE1 gene is 0.7% in gnomAD, including 33 homozygotes which is a high enough frequency 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 summary, this variant meets criteria to be classified as benign for ETHE1-related ethylmalonic encephalopathy. ETHE1 specific ACMG/AMP criteria applied: (BA1, BS2). - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 28, 2019 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 21, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 16, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 17, 2014 | 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at