Variant 14-100337086-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004184.4(WARS1):c.1230C>T(p.Asp410Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,614,032 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 28 hom. )

Consequence

WARS1
NM_004184.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0610

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 14-100337086-G-A is Benign according to our data. Variant chr14-100337086-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1879286.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-100337086-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.061 with no splicing effect.

BS2

High AC in GnomAd4 at 943 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WARS1	NM_004184.4 linkuse as main transcript	c.1230C>T	p.Asp410Asp	synonymous_variant	10/11	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.1230C>T	p.Asp410Asp	synonymous_variant	10/11	1	NM_004184.4	ENSP00000376620.2		P23381-1

Frequencies

GnomAD3 genomes

AF:

0.00616

AC:

937

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00871

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00542

AC:

1363

AN:

251460

Hom.:

AF XY:

0.00563

AC XY:

765

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00904

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00379

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.00537

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00485

AC:

7096

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

3570

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00738

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00406

Gnomad4 FIN exome

AF:

0.0162

Gnomad4 NFE exome

AF:

0.00465

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.00619

AC:

943

AN:

152286

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

501

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00888

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.00457

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00518

Hom.:

Bravo

AF:

0.00578

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00497

EpiControl

AF:

0.00599

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

WARS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 09, 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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

WARS1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.1

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)

0.0

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