rs759086547

Variant names:

• chr5-33445397-G-A
• rs759086547
• NM_152295.5:c.131G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-33445397-G-A
• chr5-33445397-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152295.5(TARS1):​c.131G>A​(p.Arg44Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TARS1 NM_152295.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23445475).

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.131G>A	p.Arg44Gln	missense	Exon 2 of 19	NP_689508.3
	TARS1	NM_001258438.2		c.131G>A	p.Arg44Gln	missense	Exon 2 of 20	NP_001245367.1	P26639-2
	TARS1	NM_001258437.1		c.131G>A	p.Arg44Gln	missense	Exon 3 of 20	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.131G>A	p.Arg44Gln	missense	Exon 2 of 19	ENSP00000265112.3	P26639-1
	TARS1	ENST00000509731.5	TSL:1	n.131G>A		non_coding_transcript_exon	Exon 2 of 19	ENSP00000427304.1	D6RJ97
	TARS1	ENST00000455217.6	TSL:2	c.131G>A	p.Arg44Gln	missense	Exon 2 of 20	ENSP00000387710.2	P26639-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250190 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460698 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726598

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39632

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111268

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.088
Sift	Benign	0.58	T
Sift4G	Benign	0.62	T
Polyphen		0.85	P
Vest4		0.54
MutPred		0.25		Loss of sheet (P = 0.0104)
MVP		0.42
MPC		0.45
ClinPred		0.81	D
GERP RS		5.2
Varity_R		0.18
gMVP		0.23
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs759086547; hg19: chr5-33445503;