rs699005

Positions:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_003680.4(YARS1):c.1218G>C(p.Leu406=) variant causes a synonymous change. The variant allele was found at a frequency of 0.098 in 1,614,056 control chromosomes in the GnomAD database, including 8,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 907 hom., cov: 31)

Exomes 𝑓: 0.097 ( 7745 hom. )

Consequence

YARS1
NM_003680.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.91

Variant links:

Genes affected

YARS1 (HGNC:12840): (tyrosyl-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. Tyrosyl-tRNA synthetase belongs to the class I tRNA synthetase family. Cytokine activities have also been observed for the human tyrosyl-tRNA synthetase, after it is split into two parts, an N-terminal fragment that harbors the catalytic site and a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine. [provided by RefSeq, Jul 2008]

YARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 1-32780201-C-G is Benign according to our data. Variant chr1-32780201-C-G is described in ClinVar as [Benign]. Clinvar id is 297151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-32780201-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YARS1	NM_003680.4 linkuse as main transcript	c.1218G>C	p.Leu406=	synonymous_variant	11/13	ENST00000373477.9	NP_003671.1
YARS1	XM_011542347.3 linkuse as main transcript	c.588G>C	p.Leu196=	synonymous_variant	9/11		XP_011540649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YARS1	ENST00000373477.9 linkuse as main transcript	c.1218G>C	p.Leu406=	synonymous_variant	11/13	1	NM_003680.4	ENSP00000362576	P1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15744

AN:

152072

Hom.:

905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0592

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0952

GnomAD3 exomes

AF:

0.104

AC:

26054

AN:

251392

Hom.:

1860

AF XY:

0.0968

AC XY:

13150

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.0563

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0607

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.0970

Gnomad OTH exome

AF:

0.0980

GnomAD4 exome

AF:

0.0974

AC:

142393

AN:

1461866

Hom.:

7745

Cov.:

AF XY:

0.0959

AC XY:

69737

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.0553

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0610

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.0993

Gnomad4 OTH exome

AF:

0.0908

GnomAD4 genome

AF:

0.104

AC:

15760

AN:

152190

Hom.:

907

Cov.:

AF XY:

0.106

AC XY:

7863

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0590

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.0947

Alfa

AF:

0.0959

Hom.:

269

Bravo

AF:

0.105

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

EpiCase

AF:

0.0966

EpiControl

AF:

0.0875

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 23, 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. -

Charcot-Marie-Tooth disease dominant intermediate C

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.7

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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