GeneBe

3-49098995-GCAGGAGA-GCAGGAGACAGGAGA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005051.3(QARS1):​c.1759-13_1759-7dupTCTCCTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,260 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000048 ( 0 hom. )

Consequence

QARS1
NM_005051.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.198

Publications

0 publications found
Variant links:
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 syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet
  • microcephaly-short stature-intellectual disability-facial dysmorphism syndrome
    Inheritance: 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
QARS1NM_005051.3 linkc.1759-13_1759-7dupTCTCCTG splice_region_variant, intron_variant Intron 18 of 23 ENST00000306125.12 NP_005042.1
QARS1NM_001272073.2 linkc.1726-13_1726-7dupTCTCCTG splice_region_variant, intron_variant Intron 18 of 23 NP_001259002.1
QARS1NR_073590.2 linkn.1734-13_1734-7dupTCTCCTG splice_region_variant, intron_variant Intron 18 of 23
QARS1XM_017006965.3 linkc.1759-13_1759-7dupTCTCCTG 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
QARS1ENST00000306125.12 linkc.1759-7_1759-6insTCTCCTG splice_region_variant, intron_variant Intron 18 of 23 1 NM_005051.3 ENSP00000307567.6

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251426
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461134
Hom.:
0
Cov.:
35
AF XY:
0.00000550
AC XY:
4
AN XY:
726928
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33472
American (AMR)
AF:
0.0000224
AC:
1
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86246
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1111310
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.511
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41422
American (AMR)
AF:
0.000131
AC:
2
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68018
Other (OTH)
AF:
0.00
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
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:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs781635166; hg19: chr3-49136428; API