3-45485607-C-T

Variant names:

• chr3-45485607-C-T
• rs7640603
• NM_015340.4:c.1019-85C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015340.4(LARS2):​c.1019-85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LARS2 NM_015340.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.1019-85C>T		intron	N/A	NP_056155.1	Q15031
	LARS2	NM_001368263.1		c.1019-85C>T		intron	N/A	NP_001355192.1	Q15031
	LARS2-AS1	NR_048543.1		n.518-1576G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARS2	ENST00000645846.2	MANE Select	c.1019-85C>T		intron	N/A	ENSP00000495093.1	Q15031
	LARS2	ENST00000265537.8	TSL:1	n.1019-85C>T		intron	N/A	ENSP00000265537.4	A0A499FJL2
	LARS2	ENST00000935381.1		c.1019-85C>T		intron	N/A	ENSP00000605440.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 578292 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 303828

African (AFR) AF: 0.00 AC: 0 AN: 16438

American (AMR) AF: 0.00 AC: 0 AN: 22874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14360

East Asian (EAS) AF: 0.00 AC: 0 AN: 32564

South Asian (SAS) AF: 0.00 AC: 0 AN: 43364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 369278

Other (OTH) AF: 0.00 AC: 0 AN: 29352

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7949

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.32

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: rs7640603; hg19: chr3-45527099;