3-49098995-GCAGGAGA-GCAGGAGACAGGAGACAGGAGA
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_005051.3(QARS1):c.1759-20_1759-7dupTCTCCTGTCTCCTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,260 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
QARS1
NM_005051.3 splice_region, intron
NM_005051.3 splice_region, intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.198
Publications
0 publications found
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]
QARS1 Gene-Disease associations (from GenCC):
- diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet
- microcephaly-short stature-intellectual disability-facial dysmorphism syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| QARS1 | NM_005051.3 | c.1759-20_1759-7dupTCTCCTGTCTCCTG | splice_region_variant, intron_variant | Intron 18 of 23 | ENST00000306125.12 | NP_005042.1 | ||
| QARS1 | NM_001272073.2 | c.1726-20_1726-7dupTCTCCTGTCTCCTG | splice_region_variant, intron_variant | Intron 18 of 23 | NP_001259002.1 | |||
| QARS1 | NR_073590.2 | n.1734-20_1734-7dupTCTCCTGTCTCCTG | splice_region_variant, intron_variant | Intron 18 of 23 | ||||
| QARS1 | XM_017006965.3 | c.1759-20_1759-7dupTCTCCTGTCTCCTG | splice_region_variant, intron_variant | Intron 18 of 22 | XP_016862454.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| QARS1 | ENST00000306125.12 | c.1759-7_1759-6insTCTCCTGTCTCCTG | splice_region_variant, intron_variant | Intron 18 of 23 | 1 | NM_005051.3 | ENSP00000307567.6 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152126
Hom.:
Cov.:
32
Gnomad AFR
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Gnomad AMI
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000159 AC: 4AN: 251426 AF XY: 0.0000221 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
251426
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad NFE exome
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461134Hom.: 0 Cov.: 35 AF XY: 0.00000825 AC XY: 6AN XY: 726928 show subpopulations
GnomAD4 exome
AF:
AC:
12
AN:
1461134
Hom.:
Cov.:
35
AF XY:
AC XY:
6
AN XY:
726928
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86246
European-Finnish (FIN)
AF:
AC:
5
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1111310
Other (OTH)
AF:
AC:
0
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.0000131 AC: 2AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152126
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74316
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41422
American (AMR)
AF:
AC:
0
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5194
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68018
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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