Variant rs9453 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004184.4(WARS1):c.1003C>T(p.Leu335Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.735 in 1,613,524 control chromosomes in the GnomAD database, including 438,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 36764 hom., cov: 30)

Exomes 𝑓: 0.74 ( 402139 hom. )

Consequence

WARS1
NM_004184.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

WARS1 (HGNC:12729): (tryptophanyl-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. Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. Tryptophanyl-tRNA synthetase (WARS) catalyzes the aminoacylation of tRNA(trp) with tryptophan and is induced by interferon. Tryptophanyl-tRNA synthetase belongs to the class I tRNA synthetase family. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

WARS1 links:

WARS1 (HGNC:):

WARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 14-100342508-G-A is Benign according to our data. Variant chr14-100342508-G-A is described in ClinVar as [Benign]. Clinvar id is 1265241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-100342508-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WARS1	NM_004184.4 linkuse as main transcript	c.1003C>T	p.Leu335Leu	synonymous_variant	9/11	ENST00000392882.7	NP_004175.2	P23381-1A0A024R6K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WARS1	ENST00000392882.7 linkuse as main transcript	c.1003C>T	p.Leu335Leu	synonymous_variant	9/11	1	NM_004184.4	ENSP00000376620.2		P23381-1

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

103899

AN:

151816

Hom.:

36739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.807

Gnomad ASJ

AF:

0.816

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.774

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.732

GnomAD3 exomes

AF:

0.757

AC:

190105

AN:

251292

Hom.:

72907

AF XY:

0.760

AC XY:

103195

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.857

Gnomad ASJ exome

AF:

0.810

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.804

Gnomad FIN exome

AF:

0.774

Gnomad NFE exome

AF:

0.737

Gnomad OTH exome

AF:

0.767

GnomAD4 exome

AF:

0.740

AC:

1081416

AN:

1461590

Hom.:

402139

Cov.:

AF XY:

0.742

AC XY:

539625

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.850

Gnomad4 ASJ exome

AF:

0.812

Gnomad4 EAS exome

AF:

0.777

Gnomad4 SAS exome

AF:

0.804

Gnomad4 FIN exome

AF:

0.778

Gnomad4 NFE exome

AF:

0.733

Gnomad4 OTH exome

AF:

0.740

GnomAD4 genome

AF:

0.684

AC:

103962

AN:

151934

Hom.:

36764

Cov.:

AF XY:

0.691

AC XY:

51334

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.493

Gnomad4 AMR

AF:

0.807

Gnomad4 ASJ

AF:

0.816

Gnomad4 EAS

AF:

0.780

Gnomad4 SAS

AF:

0.806

Gnomad4 FIN

AF:

0.774

Gnomad4 NFE

AF:

0.736

Gnomad4 OTH

AF:

0.734

Alfa

AF:

0.733

Hom.:

64038

Bravo

AF:

0.680

Asia WGS

AF:

0.778

AC:

2708

AN:

3478

EpiCase

AF:

0.744

EpiControl

AF:

0.747

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

WARS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Neuronopathy, distal hereditary motor, type 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -22

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