Genetic Variant NM_152295.5:c.330-954C>T (chr5-33452335-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_152295.5(TARS1):c.330-954C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 1,534,822 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.019 ( 96 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 71 hom. )

Consequence

TARS1
NM_152295.5 intron

Scores

Splicing: ADA: 0.00002552

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.288

Publications

0 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-33452335-C-T is Benign according to our data. Variant chr5-33452335-C-T is described in ClinVar as Benign. ClinVar VariationId is 3041502.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
TARS1	NM_152295.5	MANE Select	c.330-954C>T	intron	N/A	NP_689508.3
TARS1	NM_001258438.2		c.330-6C>T	splice_region intron	N/A	NP_001245367.1	P26639-2
TARS1	NM_001258437.1		c.330-954C>T	intron	N/A	NP_001245366.1	P26639-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TARS1	ENST00000265112.8	TSL:1 MANE Select	c.330-954C>T	intron	N/A	ENSP00000265112.3	P26639-1
TARS1	ENST00000509731.5	TSL:1	n.*283-954C>T	intron	N/A	ENSP00000427304.1	D6RJ97
TARS1	ENST00000455217.6	TSL:2	c.330-6C>T	splice_region intron	N/A	ENSP00000387710.2	P26639-2

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2911

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00505

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00407

AC:

522

AN:

128368

AF XY:

0.00302

show subpopulations

Gnomad AFR exome

AF:

0.0713

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00247

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000147

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00197

AC:

2718

AN:

1382674

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1113

AN XY:

682306

show subpopulations

African (AFR)

AF:

0.0686

AC:

2167

AN:

31584

American (AMR)

AF:

0.00280

AC:

100

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.00191

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35726

South Asian (SAS)

AF:

0.000139

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33460

Middle Eastern (MID)

AF:

0.00544

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.000109

AC:

117

AN:

1078232

Other (OTH)

AF:

0.00422

AC:

244

AN:

57886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

147

294

442

589

736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0192

AC:

2923

AN:

152148

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1370

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0673

AC:

2790

AN:

41484

American (AMR)

AF:

0.00504

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68018

Other (OTH)

AF:

0.0152

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

136

271

407

542

678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0114

Hom.:

Bravo

AF:

0.0214

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

TARS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.73

(source)

DANN

Benign

0.52

PhyloP100

-0.29

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.31

Position offset: 6

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

Publications

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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