rs761360080
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006567.5(FARS2):c.411C>A(p.Ser137Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,056 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 (★★).
Frequency
Consequence
NM_006567.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FARS2 | ENST00000274680.9 | c.411C>A | p.Ser137Arg | missense_variant | Exon 2 of 7 | 1 | NM_006567.5 | ENSP00000274680.4 | ||
FARS2 | ENST00000324331.10 | c.411C>A | p.Ser137Arg | missense_variant | Exon 2 of 7 | 1 | ENSP00000316335.5 | |||
FARS2 | ENST00000648580.1 | n.411C>A | non_coding_transcript_exon_variant | Exon 2 of 9 | ENSP00000497889.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251312Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135844
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727248
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74324
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 14 Uncertain:1
This sequence change replaces serine with arginine at codon 137 of the FARS2 protein (p.Ser137Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs761360080, ExAC 0.002%). This variant has not been reported in the literature in individuals with FARS2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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
The c.411C>A (p.S137R) alteration is located in exon 2 (coding exon 1) of the FARS2 gene. This alteration results from a C to A substitution at nucleotide position 411, causing the serine (S) at amino acid position 137 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at