5-33453263-CTTTTTTTTTTTT-CT

Variant names:

• chr5-33453263-CTTTTTTTTTTT-C
• rs35931457
• NM_152295.5:c.330-14_330-4delTTTTTTTTTTT

Variant summary

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

The NM_152295.5(TARS1):​c.330-14_330-4delTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,237,306 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: TARS1 NM_152295.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARS1	NM_152295.5	MANE Select	c.330-14_330-4delTTTTTTTTTTT		splice_region intron	N/A	NP_689508.3
	TARS1	NM_001258438.2		c.429-14_429-4delTTTTTTTTTTT		splice_region intron	N/A	NP_001245367.1	P26639-2
	TARS1	NM_001258437.1		c.330-14_330-4delTTTTTTTTTTT		splice_region intron	N/A	NP_001245366.1	P26639-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARS1	ENST00000265112.8	TSL:1 MANE Select	c.330-25_330-15delTTTTTTTTTTT		intron	N/A	ENSP00000265112.3	P26639-1
	TARS1	ENST00000509731.5	TSL:1	n.*283-25_*283-15delTTTTTTTTTTT		intron	N/A	ENSP00000427304.1	D6RJ97
	TARS1	ENST00000455217.6	TSL:2	c.429-25_429-15delTTTTTTTTTTT		intron	N/A	ENSP00000387710.2	P26639-2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000162 AC: 2 AN: 1237306 Hom.: 0 AF XY: 0.00000165 AC XY: 1 AN XY: 607486

African (AFR) AF: 0.00 AC: 0 AN: 26950

American (AMR) AF: 0.00 AC: 0 AN: 20894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19558

East Asian (EAS) AF: 0.00 AC: 0 AN: 32470

South Asian (SAS) AF: 0.00 AC: 0 AN: 54722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4380

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 992706

Other (OTH) AF: 0.00 AC: 0 AN: 50490

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs35931457; hg19: chr5-33453368;