rs115671018
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_005051.3(QARS1):c.1671G>T(p.Val557=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,614,210 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 5 hom. )
Consequence
QARS1
NM_005051.3 synonymous
NM_005051.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0780
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 Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 3-49099197-C-A is Benign according to our data. Variant chr3-49099197-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 382681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.078 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00304 (463/152324) while in subpopulation AFR AF= 0.0108 (451/41572). AF 95% confidence interval is 0.01. There are 1 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.1671G>T | p.Val557= | synonymous_variant | 18/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.1638G>T | p.Val546= | synonymous_variant | 18/24 | ||
QARS1 | XM_017006965.3 | c.1671G>T | p.Val557= | synonymous_variant | 18/23 | ||
QARS1 | NR_073590.2 | n.1646G>T | non_coding_transcript_exon_variant | 18/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.1671G>T | p.Val557= | synonymous_variant | 18/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00304 AC: 463AN: 152206Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000632 AC: 159AN: 251442Hom.: 0 AF XY: 0.000419 AC XY: 57AN XY: 135892
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GnomAD4 exome AF: 0.000276 AC: 403AN: 1461886Hom.: 5 Cov.: 35 AF XY: 0.000227 AC XY: 165AN XY: 727246
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GnomAD4 genome ? AF: 0.00304 AC: 463AN: 152324Hom.: 1 Cov.: 32 AF XY: 0.00277 AC XY: 206AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 13, 2016 | - - |
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at