rs753993545
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006567.5(FARS2):c.28G>A(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10S) has been classified as Uncertain significance.
Frequency
Consequence
NM_006567.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FARS2 | NM_006567.5 | c.28G>A | p.Ala10Thr | missense_variant | 2/7 | ENST00000274680.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FARS2 | ENST00000274680.9 | c.28G>A | p.Ala10Thr | missense_variant | 2/7 | 1 | NM_006567.5 | P1 | |
FARS2 | ENST00000324331.10 | c.28G>A | p.Ala10Thr | missense_variant | 2/7 | 1 | P1 | ||
FARS2 | ENST00000602691.1 | c.28G>A | p.Ala10Thr | missense_variant | 3/3 | 3 | |||
FARS2 | ENST00000648580.1 | c.28G>A | p.Ala10Thr | missense_variant, NMD_transcript_variant | 2/9 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250074Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135122
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461078Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726756
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2021 | This sequence change replaces alanine with threonine at codon 10 of the FARS2 protein (p.Ala10Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs753993545, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with FARS2-related conditions. 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 not expected to disrupt FARS2 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