rs1553751717
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005051.3(QARS1):c.1612del(p.Arg538GlyfsTer4) variant causes a frameshift, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
QARS1
NM_005051.3 frameshift, splice_region
NM_005051.3 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.08
Genes affected
QARS1 (HGNC:9751): (glutaminyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. In metazoans, 9 aminoacyl-tRNA synthetases specific for glutamine (gln), glutamic acid (glu), and 7 other amino acids are associated within a multienzyme complex. Although present in eukaryotes, glutaminyl-tRNA synthetase (QARS) is absent from many prokaryotes, mitochondria, and chloroplasts, in which Gln-tRNA(Gln) is formed by transamidation of the misacylated Glu-tRNA(Gln). Glutaminyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-49099345-CG-C is Pathogenic according to our data. Variant chr3-49099345-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 544142.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.1612del | p.Arg538GlyfsTer4 | frameshift_variant, splice_region_variant | 17/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.1579del | p.Arg527GlyfsTer4 | frameshift_variant, splice_region_variant | 17/24 | ||
QARS1 | XM_017006965.3 | c.1612del | p.Arg538GlyfsTer4 | frameshift_variant, splice_region_variant | 17/23 | ||
QARS1 | NR_073590.2 | n.1587del | splice_region_variant, non_coding_transcript_exon_variant | 17/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.1612del | p.Arg538GlyfsTer4 | frameshift_variant, splice_region_variant | 17/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2017 | This sequence change creates a premature translational stop signal (p.Arg538Glyfs*4) in the QARS gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with QARS-related disease. Loss-of-function variants in QARS are known to be pathogenic (PMID: 25471517). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at