chr3-49101377-T-C

Position:

chr3-49101377-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005051.3(QARS1):c.854A>G(p.Asn285Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0547 in 1,613,540 control chromosomes in the GnomAD database, including 2,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 169 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2644 hom. )

Consequence

QARS1
NM_005051.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.76

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056907833).

BP6

Variant 3-49101377-T-C is Benign according to our data. Variant chr3-49101377-T-C is described in ClinVar as [Benign]. Clinvar id is 380108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QARS1	NM_005051.3 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant	10/24	ENST00000306125.12	NP_005042.1	P47897-1B7Z840
QARS1	NM_001272073.2 linkuse as main transcript	c.821A>G	p.Asn274Ser	missense_variant	10/24		NP_001259002.1	P47897-2B7Z840
QARS1	XM_017006965.3 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant	10/23		XP_016862454.2
QARS1	NR_073590.2 linkuse as main transcript	n.829A>G		non_coding_transcript_exon_variant	10/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QARS1	ENST00000306125.12 linkuse as main transcript	c.854A>G	p.Asn285Ser	missense_variant	10/24	1	NM_005051.3	ENSP00000307567.6		P47897-1

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6062

AN:

152192

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0230

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0648

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0620

Gnomad OTH

AF:

0.0363

GnomAD3 exomes

AF:

0.0397

AC:

9981

AN:

251102

Hom.:

254

AF XY:

0.0401

AC XY:

5445

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.0496

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.0659

Gnomad NFE exome

AF:

0.0581

Gnomad OTH exome

AF:

0.0448

GnomAD4 exome

AF:

0.0563

AC:

82225

AN:

1461230

Hom.:

2644

Cov.:

AF XY:

0.0548

AC XY:

39829

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.00849

Gnomad4 AMR exome

AF:

0.0179

Gnomad4 ASJ exome

AF:

0.0521

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0145

Gnomad4 FIN exome

AF:

0.0646

Gnomad4 NFE exome

AF:

0.0649

Gnomad4 OTH exome

AF:

0.0468

GnomAD4 genome

AF:

0.0398

AC:

6063

AN:

152310

Hom.:

169

Cov.:

AF XY:

0.0389

AC XY:

2897

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.0229

Gnomad4 ASJ

AF:

0.0528

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.0648

Gnomad4 NFE

AF:

0.0620

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0538

Hom.:

404

Bravo

AF:

0.0344

TwinsUK

AF:

0.0618

AC:

229

ALSPAC

AF:

0.0682

AC:

263

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.0572

AC:

492

ExAC

AF:

0.0390

AC:

4732

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0549

EpiControl

AF:

0.0539

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2015

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.77

D;.;D;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.015

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T;T;T;T

MetaRNN

Benign

0.0057

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;.;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.4

D;D;.;.;.

REVEL

Benign

0.19

Sift

Benign

0.27

T;T;.;.;.

Sift4G

Benign

0.39

T;T;T;.;D

Polyphen

0.054

B;.;.;.;.

Vest4

0.45

MPC

0.30

ClinPred

0.040

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.69

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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