5-146114174-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020117.11(LARS1):c.3463A>G(p.Lys1155Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00044 in 1,613,962 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 5 hom. )

Consequence

LARS1
NM_020117.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.06

Variant links:

Genes affected

LARS1 (HGNC:6512): (leucyl-tRNA synthetase 1) This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu). It is found in the cytoplasm as part of a multisynthetase complex and interacts with the arginine tRNA synthetase through its C-terminal domain. A mutation in this gene was found in affected individuals with infantile liver failure syndrome 1. Alternatively spliced transcript variants of this gene have been observed. [provided by RefSeq, Dec 2015]

LARS1 links:

ENSG00000251556 (HGNC:):

ENSG00000251556 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006323129).

BP6

Variant 5-146114174-T-C is Benign according to our data. Variant chr5-146114174-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2079187.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000394 (60/152104) while in subpopulation EAS AF= 0.00813 (42/5166). AF 95% confidence interval is 0.00618. There are 2 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARS1	NM_020117.11 link	c.3463A>G	p.Lys1155Glu	missense_variant	Exon 32 of 32	ENST00000394434.7	NP_064502.9	Q9P2J5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARS1	ENST00000394434.7 link	c.3463A>G	p.Lys1155Glu	missense_variant	Exon 32 of 32	1	NM_020117.11	ENSP00000377954.2		Q9P2J5-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00811

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000513

AC:

129

AN:

251446

Hom.:

AF XY:

0.000530

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00544

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000445

AC:

650

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000474

AC XY:

345

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00960

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000198

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000394

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00813

Gnomad4 SAS

AF:

0.000832

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.000450

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000544

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LARS1-related disorder

Benign:1

Mar 09, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0092

T;.;.

Eigen

Benign

0.062

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.3

M;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

N;D;N

REVEL

Benign

0.14

Sift

Benign

0.19

T;D;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.24

MVP

0.58

MPC

0.31

ClinPred

0.033

GERP RS

5.5

Varity_R

0.11

gMVP

0.60

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