3-45394357-A-T

Position:

• chr3-45394357-A-T

Variant summary

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

The NM_015340.4(LARS2):​c.-21-76A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 767,558 control chromosomes in the GnomAD database, including 5,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2764 hom., cov: 33)
  • Exomes 𝑓: 0.066 (2270 hom.)
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0770

Genes affected

LARS2 (HGNC:17095): (leucyl-tRNA synthetase 2, mitochondrial) This gene encodes a class 1 aminoacyl-tRNA synthetase, mitochondrial leucyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-45394357-A-T is Benign according to our data. Variant chr3-45394357-A-T is described in ClinVar as [Benign]. Clinvar id is 1179492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARS2	NM_015340.4	c.-21-76A>T		intron_variant		ENST00000645846.2	NP_056155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARS2	ENST00000645846.2	c.-21-76A>T		intron_variant			NM_015340.4	ENSP00000495093	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20957 AN: 152170 Hom.: 2763 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.0430

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0661 AC: 40651 AN: 615270 Hom.: 2270 AF XY: 0.0655 AC XY: 21336 AN XY: 325594

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.0547

Gnomad4 ASJ exome AF: 0.0418

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.0675

Gnomad4 FIN exome AF: 0.0381

Gnomad4 NFE exome AF: 0.0532

Gnomad4 OTH exome AF: 0.0789

GnomAD4 genome AF: 0.138 AC: 20978 AN: 152288 Hom.: 2764 Cov.: 33 AF XY: 0.134 AC XY: 9975 AN XY: 74456

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0430

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0519

Gnomad4 OTH AF: 0.114

Alfa AF: 0.103 Hom.: 224

Bravo AF: 0.153

Asia WGS AF: 0.100 AC: 346 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	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.55

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: rs704923; hg19: chr3-45435849;