1-150497543-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025150.5(TARS2):c.1034A>G(p.His345Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 1,614,066 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. H345H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0054 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 49 hom. )

Consequence

TARS2
NM_025150.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0130

Variant links:

Genes affected

TARS2 (HGNC:30740): (threonyl-tRNA synthetase 2, mitochondrial) This gene encodes a member of the class-II aminoacyl-tRNA synthetase family. The encoded protein is a mitochondrial aminoacyl-tRNA synthetase. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 4. [provided by RefSeq, Dec 2012]

TARS2 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=0.004318863).

BP6

Variant 1-150497543-A-G is Benign according to our data. Variant chr1-150497543-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 380192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00535 (815/152288) while in subpopulation NFE AF= 0.00723 (492/68014). AF 95% confidence interval is 0.00671. There are 6 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARS2	NM_025150.5 link	c.1034A>G	p.His345Arg	missense_variant	Exon 10 of 18	ENST00000369064.8	NP_079426.2	Q9BW92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARS2	ENST00000369064.8 link	c.1034A>G	p.His345Arg	missense_variant	Exon 10 of 18	1	NM_025150.5	ENSP00000358060.3		Q9BW92-1

Frequencies

GnomAD3 genomes

AF:

0.00536

AC:

815

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00723

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00496

AC:

1245

AN:

251124

Hom.:

AF XY:

0.00481

AC XY:

653

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.00722

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00679

AC:

9932

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00662

AC XY:

4812

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00779

Gnomad4 OTH exome

AF:

0.00631

GnomAD4 genome

AF:

0.00535

AC:

815

AN:

152288

Hom.:

Cov.:

AF XY:

0.00551

AC XY:

410

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00723

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00638

Hom.:

Bravo

AF:

0.00531

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00884

AC:

ExAC

AF:

0.00509

AC:

618

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00605

EpiControl

AF:

0.00693

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Sep 19, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter