Genetic Variant TARS1:c.330-8_330-4delTTTTT (chr5-33453263-CTTTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152295.5(TARS1):c.330-8_330-4delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000365 in 1,340,776 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000095 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

TARS1
NM_152295.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.694

Publications

1 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: Uncertain_significance. The variant received 0 ACMG points.

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.330-8_330-4delTTTTT	splice_region intron	N/A	NP_689508.3
TARS1	NM_001258438.2		c.429-8_429-4delTTTTT	splice_region intron	N/A	NP_001245367.1	P26639-2
TARS1	NM_001258437.1		c.330-8_330-4delTTTTT	splice_region 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.330-25_330-21delTTTTT	intron	N/A	ENSP00000265112.3	P26639-1
TARS1	ENST00000509731.5	TSL:1	n.283-25_283-21delTTTTT	intron	N/A	ENSP00000427304.1	D6RJ97
TARS1	ENST00000455217.6	TSL:2	c.429-25_429-21delTTTTT	intron	N/A	ENSP00000387710.2	P26639-2

Frequencies

GnomAD3 genomes

AF:

0.00000950

AC:

AN:

105230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000336

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000396

AC:

489

AN:

1235546

Hom.:

AF XY:

0.000448

AC XY:

272

AN XY:

606590

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000483

AC:

AN:

26910

American (AMR)

AF:

0.00144

AC:

AN:

20832

Ashkenazi Jewish (ASJ)

AF:

0.000666

AC:

AN:

19524

East Asian (EAS)

AF:

0.000340

AC:

AN:

32388

South Asian (SAS)

AF:

0.00141

AC:

AN:

54526

European-Finnish (FIN)

AF:

0.000599

AC:

AN:

35056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4372

European-Non Finnish (NFE)

AF:

0.000306

AC:

303

AN:

991526

Other (OTH)

AF:

0.000417

AC:

AN:

50412

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.258

Heterozygous variant carriers

122

182

243

304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000950

AC:

AN:

105230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

49638

show subpopulations

African (AFR)

AF:

0.0000336

AC:

AN:

29764

American (AMR)

AF:

0.00

AC:

AN:

9528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

2676

South Asian (SAS)

AF:

0.00

AC:

AN:

2934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

182

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50862

Other (OTH)

AF:

0.00

AC:

AN:

1392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.69

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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5-33453263-CTTTTTTTTTTTT-CTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over