1-150487872-C-T

Variant names:

• chr1-150487872-C-T
• rs2275245
• NM_025150.5:c.81C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_025150.5(TARS2):​c.81C>T​(p.Thr27Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,612,718 control chromosomes in the GnomAD database, including 1,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (432 hom., cov: 32)
  • Exomes 𝑓: 0.012 (1313 hom.)
• Consequence: TARS2 NM_025150.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.337
• Publications: 6 publications found

Genes affected

TARS2 (HGNC:30740): (threonyl-tRNA synthetase 2, mitochondrial) This gene encodes a member of the class-II aminoacyl-tRNA synthetase family. The encoded protein is a mitochondrial aminoacyl-tRNA synthetase. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 4. [provided by RefSeq, Dec 2012]

TARS2 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 21

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-150487872-C-T is Benign according to our data. Variant chr1-150487872-C-T is described in ClinVar as Benign. ClinVar VariationId is 380568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.337 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025150.5. 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
	TARS2	NM_025150.5	MANE Select	c.81C>T	p.Thr27Thr	synonymous	Exon 2 of 18	NP_079426.2
	TARS2	NM_001271895.2		c.81C>T	p.Thr27Thr	synonymous	Exon 2 of 16	NP_001258824.1	U3KQG0
	TARS2	NM_001271896.2		c.81C>T	p.Thr27Thr	synonymous	Exon 2 of 14	NP_001258825.1	Q9BW92-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARS2	ENST00000369064.8	TSL:1 MANE Select	c.81C>T	p.Thr27Thr	synonymous	Exon 2 of 18	ENSP00000358060.3	Q9BW92-1
	TARS2	ENST00000606933.5	TSL:1	c.81C>T	p.Thr27Thr	synonymous	Exon 2 of 16	ENSP00000475847.1	U3KQG0
	TARS2	ENST00000895426.1		c.81C>T	p.Thr27Thr	synonymous	Exon 2 of 17	ENSP00000565485.1

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7201 AN: 152044 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.0607

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0359

GnomAD2 exomes AF: 0.0386 AC: 9686 AN: 250824 AF XY: 0.0299

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.00787

Gnomad EAS exome AF: 0.0508

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000794

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0120 AC: 17455 AN: 1460556 Hom.: 1313 Cov.: 31 AF XY: 0.0106 AC XY: 7719 AN XY: 726586

African (AFR) AF: 0.131 AC: 4376 AN: 33436

American (AMR) AF: 0.165 AC: 7344 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00728 AC: 190 AN: 26106

East Asian (EAS) AF: 0.0949 AC: 3767 AN: 39696

South Asian (SAS) AF: 0.00356 AC: 307 AN: 86190

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53414

Middle Eastern (MID) AF: 0.00731 AC: 36 AN: 4928

European-Non Finnish (NFE) AF: 0.000544 AC: 605 AN: 1111866

Other (OTH) AF: 0.0137 AC: 828 AN: 60284

GnomAD4 genome AF: 0.0474 AC: 7218 AN: 152162 Hom.: 432 Cov.: 32 AF XY: 0.0480 AC XY: 3568 AN XY: 74392

African (AFR) AF: 0.132 AC: 5466 AN: 41472

American (AMR) AF: 0.0822 AC: 1256 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3468

East Asian (EAS) AF: 0.0604 AC: 313 AN: 5180

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68016

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0212 Hom.: 172

Bravo AF: 0.0609

Asia WGS AF: 0.0340 AC: 118 AN: 3478

EpiCase AF: 0.000982

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	TARS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		-0.34
PromoterAI		0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2275245; hg19: chr1-150460348; COSMIC: COSV64695557; COSMIC: COSV64695557;