rs746082442
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001985.3(ETFB):āc.122T>Cā(p.Phe41Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 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 Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. F41F) has been classified as Likely benign.
Frequency
Consequence
NM_001985.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETFB | NM_001985.3 | c.122T>C | p.Phe41Ser | missense_variant | 2/6 | ENST00000309244.9 | |
ETFB | NM_001014763.1 | c.395T>C | p.Phe132Ser | missense_variant | 1/5 | ||
ETFB | XM_024451418.2 | c.11T>C | p.Phe4Ser | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETFB | ENST00000309244.9 | c.122T>C | p.Phe41Ser | missense_variant | 2/6 | 1 | NM_001985.3 | P1 | |
ETFB | ENST00000354232.8 | c.395T>C | p.Phe132Ser | missense_variant | 1/5 | 1 | |||
ETFB | ENST00000596253.1 | c.122T>C | p.Phe41Ser | missense_variant | 2/5 | 3 | |||
ETFB | ENST00000593992.1 | n.145T>C | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251382Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135878
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Multiple acyl-CoA dehydrogenase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | This variant has not been reported in the literature in individuals affected with ETFB-related conditions. This variant is present in population databases (rs746082442, gnomAD 0.003%). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 41 of the ETFB protein (p.Phe41Ser). ClinVar contains an entry for this variant (Variation ID: 459958). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ETFB protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at