rs142517070

Positions:

chr3-49101858-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005051.3(QARS1):c.673C>T(p.Arg225Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,612,400 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 15 hom. )

Consequence

QARS1
NM_005051.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.27

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:

QARS1 (HGNC:):

QARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00934428).

BP6

Variant 3-49101858-G-A is Benign according to our data. Variant chr3-49101858-G-A is described in ClinVar as [Benign]. Clinvar id is 477843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49101858-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QARS1	NM_005051.3 linkuse as main transcript	c.673C>T	p.Arg225Trp	missense_variant	8/24	ENST00000306125.12	NP_005042.1	P47897-1B7Z840
QARS1	NM_001272073.2 linkuse as main transcript	c.640C>T	p.Arg214Trp	missense_variant	8/24		NP_001259002.1	P47897-2B7Z840
QARS1	XM_017006965.3 linkuse as main transcript	c.673C>T	p.Arg225Trp	missense_variant	8/23		XP_016862454.2
QARS1	NR_073590.2 linkuse as main transcript	n.648C>T		non_coding_transcript_exon_variant	8/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QARS1	ENST00000306125.12 linkuse as main transcript	c.673C>T	p.Arg225Trp	missense_variant	8/24	1	NM_005051.3	ENSP00000307567.6		P47897-1

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

287

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00211

AC:

523

AN:

247486

Hom.:

AF XY:

0.00212

AC XY:

284

AN XY:

133888

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.000465

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000973

AC:

1421

AN:

1460066

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

668

AN XY:

726230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0192

Gnomad4 NFE exome

AF:

0.000317

Gnomad4 OTH exome

AF:

0.000630

GnomAD4 genome

AF:

0.00188

AC:

287

AN:

152334

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000296

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00156

AC:

189

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2018

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 15, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

T;.;T;T;T;.;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D

MetaRNN

Benign

0.0093

T;T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.8

M;.;.;.;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.8

N;N;.;.;.;N;.

REVEL

Uncertain

0.29

Sift

Uncertain

0.016

D;D;.;.;.;D;.

Sift4G

Uncertain

0.018

D;D;D;T;.;T;D

Polyphen

1.0

D;.;.;.;.;.;.

Vest4

0.73

MVP

0.55

MPC

1.1

ClinPred

0.060

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.16

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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