rs761251190
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_005051.3(QARS1):c.704-10G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 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 (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
QARS1
NM_005051.3 splice_polypyrimidine_tract, intron
NM_005051.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001552
2
Clinical Significance
Conservation
PhyloP100: 0.0220
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 3-49101715-C-G is Benign according to our data. Variant chr3-49101715-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 415518.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.704-10G>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000306125.12 | |||
QARS1 | NM_001272073.2 | c.671-10G>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
QARS1 | XM_017006965.3 | c.704-10G>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
QARS1 | NR_073590.2 | n.679-10G>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.704-10G>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251056Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135692
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461758Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727186
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 15, 2016 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at