5-33446950-C-T

Variant names:

• chr5-33446950-C-T
• rs7705177
• NM_152295.5:c.138+1546C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152295.5(TARS1):​c.138+1546C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,942 control chromosomes in the GnomAD database, including 5,065 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (5065 hom., cov: 32)
• Consequence: TARS1 NM_152295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 4 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 Submitted by: G2P
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARS1	NM_152295.5	c.138+1546C>T		intron_variant	Intron 2 of 18	ENST00000265112.8	NP_689508.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARS1	ENST00000265112.8	c.138+1546C>T		intron_variant	Intron 2 of 18	1	NM_152295.5	ENSP00000265112.3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33896 AN: 151824 Hom.: 5055 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 33935 AN: 151942 Hom.: 5065 Cov.: 32 AF XY: 0.222 AC XY: 16475 AN XY: 74268

African (AFR) AF: 0.429 AC: 17782 AN: 41412

American (AMR) AF: 0.135 AC: 2058 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3468

East Asian (EAS) AF: 0.0275 AC: 142 AN: 5156

South Asian (SAS) AF: 0.259 AC: 1247 AN: 4810

European-Finnish (FIN) AF: 0.164 AC: 1728 AN: 10544

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10134 AN: 67970

Other (OTH) AF: 0.193 AC: 406 AN: 2108

Alfa AF: 0.208 Hom.: 697

Bravo AF: 0.226

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.21
DANN	Benign	0.61
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7705177; hg19: chr5-33447056;