rs374202707
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_005051.3(QARS1):āc.1200C>Gā(p.Ala400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00012 ( 0 hom., cov: 33)
Exomes š: 0.00022 ( 0 hom. )
Consequence
QARS1
NM_005051.3 synonymous
NM_005051.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.39
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 3-49100056-G-C is Benign according to our data. Variant chr3-49100056-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 415514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.39 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.1200C>G | p.Ala400= | synonymous_variant | 14/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.1167C>G | p.Ala389= | synonymous_variant | 14/24 | ||
QARS1 | XM_017006965.3 | c.1200C>G | p.Ala400= | synonymous_variant | 14/23 | ||
QARS1 | NR_073590.2 | n.1175C>G | non_coding_transcript_exon_variant | 14/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.1200C>G | p.Ala400= | synonymous_variant | 14/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251486Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135916
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GnomAD4 exome AF: 0.000216 AC: 316AN: 1461894Hom.: 0 Cov.: 35 AF XY: 0.000187 AC XY: 136AN XY: 727248
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74342
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | QARS1: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2021 | - - |
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at