rs4945276

chr11-78453938-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024678.6(NARS2):c.1165-10180A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,142 control chromosomes in the GnomAD database, including 5,433 homozygotes. 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: 𝑓 0.24 (5433 hom., cov: 32)
• Consequence: NARS2 NM_024678.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487

Genes affected

NARS2 (HGNC:26274): (asparaginyl-tRNA synthetase 2, mitochondrial) This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of asparagine to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 24 (COXPD24). [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NARS2	NM_024678.6	c.1165-10180A>C		intron_variant		ENST00000281038.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NARS2	ENST00000281038.10	c.1165-10180A>C		intron_variant		1	NM_024678.6	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36549 AN: 152024 Hom.: 5435 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.240 AC: 36539 AN: 152142 Hom.: 5433 Cov.: 32 AF XY: 0.236 AC XY: 17593 AN XY: 74392

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.0857

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.274

Alfa AF: 0.314 Hom.: 11277

Bravo AF: 0.236

Asia WGS AF: 0.121 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.6
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4945276; hg19: chr11-78164984;