rs370983000
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006567.5(FARS2):c.1069C>T(p.Leu357Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,611,726 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 (★★).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FARS2 | NM_006567.5 | c.1069C>T | p.Leu357Phe | missense_variant | 6/7 | ENST00000274680.9 | NP_006558.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FARS2 | ENST00000274680.9 | c.1069C>T | p.Leu357Phe | missense_variant | 6/7 | 1 | NM_006567.5 | ENSP00000274680.4 | ||
FARS2 | ENST00000324331.10 | c.1069C>T | p.Leu357Phe | missense_variant | 6/7 | 1 | ENSP00000316335.5 | |||
FARS2 | ENST00000648580.1 | n.1069C>T | non_coding_transcript_exon_variant | 6/9 | ENSP00000497889.1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000841 AC: 21AN: 249798Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135144
GnomAD4 exome AF: 0.000222 AC: 324AN: 1459552Hom.: 0 Cov.: 29 AF XY: 0.000220 AC XY: 160AN XY: 726206
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74338
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 07, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 357 of the FARS2 protein (p.Leu357Phe). This variant is present in population databases (rs370983000, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 540537). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 14, 2023 | The c.1069C>T (p.L357F) alteration is located in exon 6 (coding exon 5) of the FARS2 gene. This alteration results from a C to T substitution at nucleotide position 1069, causing the leucine (L) at amino acid position 357 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at