chr6-5613197-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The ENST00000274680.9(FARS2):āc.1094A>Gā(p.Asn365Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,238 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 ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N365H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000274680.9 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FARS2 | NM_006567.5 | c.1094A>G | p.Asn365Ser | 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.1094A>G | p.Asn365Ser | missense_variant | 6/7 | 1 | NM_006567.5 | ENSP00000274680 | P1 | |
FARS2 | ENST00000324331.10 | c.1094A>G | p.Asn365Ser | missense_variant | 6/7 | 1 | ENSP00000316335 | P1 | ||
FARS2 | ENST00000648580.1 | c.1094A>G | p.Asn365Ser | missense_variant, NMD_transcript_variant | 6/9 | ENSP00000497889 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250986Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135692
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461022Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 726874
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74362
ClinVar
Submissions by phenotype
Combined oxidative phosphorylation defect type 14 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 05, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 365 of the FARS2 protein (p.Asn365Ser). This variant is present in population databases (rs373811519, gnomAD 0.006%). 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: 587666). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Jun 13, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at