chr1-150487417-CTGTT-C

Position:

• chr1-150487417-CTGTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The 1-150487417-CTGTT-C 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARS2	NM_025150.5			5_prime_UTR_variant	1/18	ENST00000369064.8	NP_079426.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARS2	ENST00000369064.8			5_prime_UTR_variant	1/18	1	NM_025150.5	ENSP00000358060	P1

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

GnomAD3 exomes AF: 0.0385 AC: 9673 AN: 250966 Hom.: 811 AF XY: 0.0298 AC XY: 4044 AN XY: 135638

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 SAS exome AF: 0.00366

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

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.00731

Gnomad4 EAS exome AF: 0.0948

Gnomad4 SAS exome AF: 0.00362

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000545

Gnomad4 OTH exome AF: 0.0145

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

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0830

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.0602

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0234 Hom.: 47

Bravo AF: 0.0615

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 01, 2016	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 16, 2016	- -

not specified Benign:1

Benign, flagged submission

clinical testing

GeneDx

Jan 30, 2017

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

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: rs3840448; hg19: chr1-150459893;