rs199673198
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000126.4(ETFA):āc.442A>Gā(p.Ile148Val) variant causes a missense change. The variant allele was found at a frequency of 0.000184 in 1,607,250 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00013 ( 0 hom., cov: 32)
Exomes š: 0.00019 ( 2 hom. )
Consequence
ETFA
NM_000126.4 missense
NM_000126.4 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 4.79
Genes affected
ETFA (HGNC:3481): (electron transfer flavoprotein subunit alpha) ETFA participates in catalyzing the initial step of the mitochondrial fatty acid beta-oxidation. It shuttles electrons between primary flavoprotein dehydrogenases and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. Defects in electron-transfer-flavoprotein have been implicated in type II glutaricaciduria in which multiple acyl-CoA dehydrogenase deficiencies result in large excretion of glutaric, lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.025193602).
BP6
?
Variant 15-76287855-T-C is Benign according to our data. Variant chr15-76287855-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 235646.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000131 (20/152338) while in subpopulation SAS AF= 0.00207 (10/4822). AF 95% confidence interval is 0.00112. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETFA | NM_000126.4 | c.442A>G | p.Ile148Val | missense_variant | 5/12 | ENST00000557943.6 | |
ETFA | NM_001127716.2 | c.295A>G | p.Ile99Val | missense_variant | 4/11 | ||
ETFA | XR_007064434.1 | n.523A>G | non_coding_transcript_exon_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETFA | ENST00000557943.6 | c.442A>G | p.Ile148Val | missense_variant | 5/12 | 1 | NM_000126.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152220Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000430 AC: 108AN: 251386Hom.: 1 AF XY: 0.000611 AC XY: 83AN XY: 135870
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GnomAD4 exome AF: 0.000189 AC: 275AN: 1454912Hom.: 2 Cov.: 28 AF XY: 0.000269 AC XY: 195AN XY: 724280
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GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74498
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 26, 2015 | - - |
Multiple acyl-CoA dehydrogenase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Glutaric acidemia type 2A Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
Sift
Benign
T;T;T;D;D
Sift4G
Uncertain
D;T;T;D;.
Polyphen
B;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at