NM_025150.5:c.191C>T

Variant names:

• chr1-150487982-C-T
• rs1287843869
• NM_025150.5:c.191C>T

Variant summary

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

The NM_025150.5(TARS2):​c.191C>T​(p.Ser64Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S64P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TARS2 NM_025150.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 1 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: 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=0.08709335).

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.191C>T	p.Ser64Leu	missense	Exon 2 of 18	NP_079426.2
	TARS2	NM_001271895.2		c.191C>T	p.Ser64Leu	missense	Exon 2 of 16	NP_001258824.1	U3KQG0
	TARS2	NM_001271896.2		c.191C>T	p.Ser64Leu	missense	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.191C>T	p.Ser64Leu	missense	Exon 2 of 18	ENSP00000358060.3	Q9BW92-1
	TARS2	ENST00000606933.5	TSL:1	c.191C>T	p.Ser64Leu	missense	Exon 2 of 16	ENSP00000475847.1	U3KQG0
	TARS2	ENST00000895426.1		c.191C>T	p.Ser64Leu	missense	Exon 2 of 17	ENSP00000565485.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.056	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.30
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.098
Sift	Benign	0.075	T
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.41		Loss of disorder (P = 0.0345)
MVP		0.20
MPC		0.40
ClinPred		0.69	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.66
Mutation Taster		=92/8	polymorphism

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: rs1287843869; hg19: chr1-150460458;