rs141305584

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152295.5(TARS1):c.284C>A(p.Ala95Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00833 in 1,613,540 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 54 hom. )

Consequence

TARS1
NM_152295.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.41

Publications

11 publications found

Variant links:

Genes affected

TARS1 (HGNC:11572): (threonyl-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. Threonyl-tRNA synthetase belongs to the class-II aminoacyl-tRNA synthetase family [provided by RefSeq, Jul 2008]

TARS1 Gene-Disease associations (from GenCC):

trichothiodystrophy 7, nonphotosensitive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P
trichothiodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007931799).

BP6

Variant 5-33448686-C-A is Benign according to our data. Variant chr5-33448686-C-A is described in ClinVar as Benign. ClinVar VariationId is 2655386.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152295.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TARS1	NM_152295.5	MANE Select	c.284C>A	p.Ala95Glu	missense	Exon 3 of 19	NP_689508.3
TARS1	NM_001258438.2		c.284C>A	p.Ala95Glu	missense	Exon 3 of 20	NP_001245367.1	P26639-2
TARS1	NM_001258437.1		c.284C>A	p.Ala95Glu	missense	Exon 4 of 20	NP_001245366.1	P26639-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TARS1	ENST00000265112.8	TSL:1 MANE Select	c.284C>A	p.Ala95Glu	missense	Exon 3 of 19	ENSP00000265112.3	P26639-1
TARS1	ENST00000509731.5	TSL:1	n.*237C>A		non_coding_transcript_exon	Exon 4 of 19	ENSP00000427304.1	D6RJ97
TARS1	ENST00000509731.5	TSL:1	n.*237C>A		3_prime_UTR	Exon 4 of 19	ENSP00000427304.1	D6RJ97

Frequencies

GnomAD3 genomes

AF:

0.00597

AC:

908

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00533

AC:

1337

AN:

250924

AF XY:

0.00532

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00988

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00858

AC:

12531

AN:

1461316

Hom.:

Cov.:

AF XY:

0.00837

AC XY:

6081

AN XY:

726956

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

33460

American (AMR)

AF:

0.00226

AC:

101

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00195

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00115

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00154

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0106

AC:

11809

AN:

1111718

Other (OTH)

AF:

0.00560

AC:

338

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

619

1238

1858

2477

3096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

438

876

1314

1752

2190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00596

AC:

907

AN:

152224

Hom.:

Cov.:

AF XY:

0.00538

AC XY:

400

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41528

American (AMR)

AF:

0.00242

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0110

AC:

748

AN:

68010

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00835

Hom.:

Bravo

AF:

0.00556

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0101

AC:

ExAC

AF:

0.00520

AC:

631

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00972

EpiControl

AF:

0.00949

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

TARS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.5

PhyloP100

1.4

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.26

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.038

Polyphen

0.98

Vest4

0.47

MVP

0.63

MPC

0.71

ClinPred

0.022

GERP RS

5.1

Varity_R

0.95

gMVP

0.89

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over