1-150494892-C-T

Variant names:

• chr1-150494892-C-T
• rs11205384
• NM_025150.5:c.775-1590C>T

Variant summary

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

The NM_025150.5(TARS2):​c.775-1590C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,240 control chromosomes in the GnomAD database, including 25,790 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 0.58 (25790 hom., cov: 30)
• Consequence: TARS2 NM_025150.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 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.775-1590C>T		intron	N/A	NP_079426.2
	TARS2	NM_001271895.2		c.774+2403C>T		intron	N/A	NP_001258824.1	U3KQG0
	TARS2	NM_001271896.2		c.631-2638C>T		intron	N/A	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.775-1590C>T		intron	N/A	ENSP00000358060.3	Q9BW92-1
	TARS2	ENST00000606933.5	TSL:1	c.774+2403C>T		intron	N/A	ENSP00000475847.1	U3KQG0
	TARS2	ENST00000895426.1		c.775-1590C>T		intron	N/A	ENSP00000565485.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87634 AN: 151122 Hom.: 25769 Cov.: 30

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.580 AC: 87694 AN: 151240 Hom.: 25790 Cov.: 30 AF XY: 0.573 AC XY: 42353 AN XY: 73868

African (AFR) AF: 0.588 AC: 24283 AN: 41266

American (AMR) AF: 0.495 AC: 7536 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2180 AN: 3450

East Asian (EAS) AF: 0.298 AC: 1521 AN: 5100

South Asian (SAS) AF: 0.414 AC: 1979 AN: 4780

European-Finnish (FIN) AF: 0.654 AC: 6823 AN: 10428

Middle Eastern (MID) AF: 0.476 AC: 137 AN: 288

European-Non Finnish (NFE) AF: 0.614 AC: 41571 AN: 67690

Other (OTH) AF: 0.555 AC: 1166 AN: 2102

Alfa AF: 0.600 Hom.: 3372

Bravo AF: 0.570

Asia WGS AF: 0.424 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.44
PhyloP100		-3.1
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: rs11205384; hg19: chr1-150467368;