rs119458969
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_000126.4(ETFA):āc.470T>Gā(p.Val157Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,610,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ā ).
Frequency
Consequence
NM_000126.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ETFA | NM_000126.4 | c.470T>G | p.Val157Gly | missense_variant | Exon 6 of 12 | ENST00000557943.6 | NP_000117.1 | |
ETFA | NM_001127716.2 | c.323T>G | p.Val108Gly | missense_variant | Exon 5 of 11 | NP_001121188.1 | ||
ETFA | XR_007064434.1 | n.551T>G | non_coding_transcript_exon_variant | Exon 6 of 12 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251054Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135664
GnomAD4 exome AF: 0.00000754 AC: 11AN: 1458694Hom.: 0 Cov.: 29 AF XY: 0.00000964 AC XY: 7AN XY: 725872
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Multiple acyl-CoA dehydrogenase deficiency Pathogenic:3
Variant summary: ETFA c.470T>G (p.Val157Gly) results in a non-conservative amino acid change located in the N-terminal domain (IPR014730) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251054 control chromosomes. c.470T>G has been reported in the literature in at least two individuals affected with Glutaric Aciduria, Type 2a (Indo_1991, Freneaux_1992, Schiff_2006). These data indicate that the variant may be associated with disease. These publications also reported that the ETFA protein was almost undetectable and had a severely reduced enzyme activity in patient derived fibroblasts (Indo_1991, Freneaux_1992, Schiff_2006). The following publications have been ascertained in the context of this evaluation (PMID: 16546179, 33450351, 20674745, 16510302, 1430199, 1882842, 23867278). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. -
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Glutaric acidemia IIa Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at