rs3840448

Variant names:

• chr1-150487416-TCTGT-TC
• NM_025150.5:c.-33_-31delTGT

Your query was ambiguous. Multiple possible variants found:

• chr1-150487417-CTGTT-C
• chr1-150487417-CTGTT-CTGTTTGTT

Variant summary

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

The NM_025150.5(TARS2):​c.-33_-31delTGT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TARS2 NM_025150.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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_-31delTGT		5_prime_UTR	Exon 1 of 18	NP_079426.2
	TARS2	NM_025150.5	MANE Select	c.-33_-31delTGT		non_coding_transcript	N/A	NP_079426.2
	TARS2	NM_001271895.2		c.-33_-31delTGT		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.-32_-30delGTT		5_prime_UTR	Exon 1 of 18	ENSP00000358060.3	Q9BW92-1
	TARS2	ENST00000606933.5	TSL:1	c.-32_-30delGTT		5_prime_UTR	Exon 1 of 16	ENSP00000475847.1	U3KQG0
	TARS2	ENST00000606933.5	TSL:1	c.-32_-30delGTT		non_coding_transcript	N/A	ENSP00000475847.1	U3KQG0

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-150459892;