1-150487692-A-G

Position:

• chr1-150487692-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025150.5(TARS2):​c.67-166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,926 control chromosomes in the GnomAD database, including 28,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.61 (28423 hom., cov: 31)
• Consequence: TARS2 NM_025150.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-150487692-A-G is Benign according to our data. Variant chr1-150487692-A-G is described in ClinVar as [Benign]. Clinvar id is 680801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARS2	NM_025150.5	c.67-166A>G		intron_variant		ENST00000369064.8	NP_079426.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARS2	ENST00000369064.8	c.67-166A>G		intron_variant		1	NM_025150.5	ENSP00000358060	P1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91962 AN: 151806 Hom.: 28379 Cov.: 31

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.606 AC: 92052 AN: 151926 Hom.: 28423 Cov.: 31 AF XY: 0.599 AC XY: 44454 AN XY: 74250

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.575

Alfa AF: 0.433 Hom.: 942

Bravo AF: 0.598

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275246; hg19: chr1-150460168;