3-45488704-C-T

Variant names:

• chr3-45488704-C-T
• rs144183054
• NM_015340.4:c.1131C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015340.4(LARS2):​c.1131C>T​(p.Pro377Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,601,306 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (208 hom.)
• Consequence: LARS2 NM_015340.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.383
• Publications: 1 publications found

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]

LARS2-AS1 (HGNC:40796): (LARS2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 3-45488704-C-T is Benign according to our data. Variant chr3-45488704-C-T is described in ClinVar as Benign. ClinVar VariationId is 226692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.383 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015340.4. 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
	LARS2	NM_015340.4	MANE Select	c.1131C>T	p.Pro377Pro	synonymous	Exon 12 of 22	NP_056155.1	Q15031
	LARS2	NM_001368263.1		c.1131C>T	p.Pro377Pro	synonymous	Exon 11 of 21	NP_001355192.1	Q15031
	LARS2-AS1	NR_048543.1		n.518-4673G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARS2	ENST00000645846.2	MANE Select	c.1131C>T	p.Pro377Pro	synonymous	Exon 12 of 22	ENSP00000495093.1	Q15031
	LARS2	ENST00000265537.8	TSL:1	n.1131C>T		non_coding_transcript_exon	Exon 12 of 23	ENSP00000265537.4	A0A499FJL2
	LARS2	ENST00000935381.1		c.1131C>T	p.Pro377Pro	synonymous	Exon 12 of 23	ENSP00000605440.1

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 806 AN: 152178 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.0127 AC: 3184 AN: 251346 AF XY: 0.00936

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.0894

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00287 AC: 4160 AN: 1449010 Hom.: 208 Cov.: 28 AF XY: 0.00241 AC XY: 1739 AN XY: 721794

African (AFR) AF: 0.000663 AC: 22 AN: 33178

American (AMR) AF: 0.0860 AC: 3844 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.000782 AC: 31 AN: 39624

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000400 AC: 44 AN: 1100244

Other (OTH) AF: 0.00322 AC: 193 AN: 60006

GnomAD4 genome AF: 0.00533 AC: 812 AN: 152296 Hom.: 20 Cov.: 33 AF XY: 0.00576 AC XY: 429 AN XY: 74458

African (AFR) AF: 0.00113 AC: 47 AN: 41558

American (AMR) AF: 0.0479 AC: 733 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68038

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.00155 Hom.: 1

Bravo AF: 0.0107

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	1	LARS2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.1
DANN	Benign	0.72
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs144183054; hg19: chr3-45530196;