3-49098368-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005051.3(QARS1):c.2069G>A(p.Arg690His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R690C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005051.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.2069G>A | p.Arg690His | missense_variant | 21/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.2036G>A | p.Arg679His | missense_variant | 21/24 | ||
QARS1 | XM_017006965.3 | c.2069G>A | p.Arg690His | missense_variant | 21/23 | ||
QARS1 | NR_073590.2 | n.2044G>A | non_coding_transcript_exon_variant | 21/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.2069G>A | p.Arg690His | missense_variant | 21/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152164Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251480Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135916
GnomAD4 exome AF: 0.0000629 AC: 92AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000729 AC XY: 53AN XY: 727246
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152282Hom.: 0 Cov.: 31 AF XY: 0.0000671 AC XY: 5AN XY: 74466
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 21, 2021 | This sequence change replaces arginine with histidine at codon 690 of the QARS protein (p.Arg690His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs201781920, ExAC 0.08%). This variant has not been reported in the literature in individuals affected with QARS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 | GeneDx | Feb 04, 2020 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at