1-150487417-CTGTT-C

Variant names:

• chr1-150487417-CTGTT-C
• rs3840448
• NM_025150.5:c.-33_-30delTGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025150.5(TARS2):​c.-33_-30delTGTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,613,820 control chromosomes in the GnomAD database, including 1,735 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (427 hom., cov: 32)
  • Exomes 𝑓: 0.012 (1308 hom.)
• Consequence: TARS2 NM_025150.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.299
• Publications: 4 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 -10 ACMG points.

• BP6: Variant 1-150487417-CTGTT-C is Benign according to our data. Variant chr1-150487417-CTGTT-C is described in ClinVar as Benign. ClinVar VariationId is 517079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 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.-33_-30delTGTT		5_prime_UTR	Exon 1 of 18	NP_079426.2
	TARS2	NM_025150.5	MANE Select	c.-33_-30delTGTT		non_coding_transcript	N/A	NP_079426.2
	TARS2	NM_001271895.2		c.-33_-30delTGTT		5_prime_UTR	Exon 1 of 16	NP_001258824.1	U3KQG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARS2	ENST00000369064.8	TSL:1 MANE Select	c.-31_-28delTTTG		5_prime_UTR	Exon 1 of 18	ENSP00000358060.3	Q9BW92-1
	TARS2	ENST00000606933.5	TSL:1	c.-31_-28delTTTG		5_prime_UTR	Exon 1 of 16	ENSP00000475847.1	U3KQG0
	TARS2	ENST00000895426.1		c.-31_-28delTTTG		5_prime_UTR	Exon 1 of 17	ENSP00000565485.1

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7257 AN: 152086 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0363

GnomAD2 exomes AF: 0.0385 AC: 9673 AN: 250966 AF XY: 0.0298

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.00786

Gnomad EAS exome AF: 0.0509

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000811

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0120 AC: 17567 AN: 1461616 Hom.: 1308 AF XY: 0.0107 AC XY: 7758 AN XY: 727116

African (AFR) AF: 0.132 AC: 4428 AN: 33464

American (AMR) AF: 0.164 AC: 7339 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00731 AC: 191 AN: 26132

East Asian (EAS) AF: 0.0948 AC: 3763 AN: 39700

South Asian (SAS) AF: 0.00362 AC: 312 AN: 86252

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5768

European-Non Finnish (NFE) AF: 0.000545 AC: 606 AN: 1111832

Other (OTH) AF: 0.0145 AC: 877 AN: 60386

GnomAD4 genome AF: 0.0478 AC: 7275 AN: 152204 Hom.: 427 Cov.: 32 AF XY: 0.0483 AC XY: 3592 AN XY: 74410

African (AFR) AF: 0.133 AC: 5511 AN: 41510

American (AMR) AF: 0.0830 AC: 1269 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.0602 AC: 311 AN: 5162

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68022

Other (OTH) AF: 0.0360 AC: 76 AN: 2114

Alfa AF: 0.0234 Hom.: 47

Bravo AF: 0.0615

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=300/0	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: rs3840448; hg19: chr1-150459893;