rs113144521

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005051.3(QARS1):c.1635A>G(p.Gln545Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,614,086 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 15 hom. )

Consequence

QARS1
NM_005051.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.95

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 3-49099233-T-C is Benign according to our data. Variant chr3-49099233-T-C is described in ClinVar as [Benign]. Clinvar id is 240091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49099233-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.95 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00659 (1003/152248) while in subpopulation AFR AF= 0.0226 (939/41548). AF 95% confidence interval is 0.0214. There are 11 homozygotes in gnomad4. There are 485 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QARS1	NM_005051.3 link	c.1635A>G	p.Gln545Gln	synonymous_variant	Exon 18 of 24	ENST00000306125.12	NP_005042.1	P47897-1B7Z840
QARS1	NM_001272073.2 link	c.1602A>G	p.Gln534Gln	synonymous_variant	Exon 18 of 24		NP_001259002.1	P47897-2B7Z840
QARS1	XM_017006965.3 link	c.1635A>G	p.Gln545Gln	synonymous_variant	Exon 18 of 23		XP_016862454.2
QARS1	NR_073590.2 link	n.1610A>G		non_coding_transcript_exon_variant	Exon 18 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QARS1	ENST00000306125.12 link	c.1635A>G	p.Gln545Gln	synonymous_variant	Exon 18 of 24	1	NM_005051.3	ENSP00000307567.6		P47897-1

Frequencies

GnomAD3 genomes

AF:

0.00659

AC:

1003

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00196

AC:

492

AN:

251424

Hom.:

AF XY:

0.00152

AC XY:

207

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00163

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000742

AC:

1085

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000682

AC XY:

496

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0233

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00659

AC:

1003

AN:

152248

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

485

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00289

Hom.:

Bravo

AF:

0.00739

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 21, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Feb 16, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.9

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over