11-78450406-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024678.6(NARS2):​c.1165-6648T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,028 control chromosomes in the GnomAD database, including 4,181 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 0.22 ( 4181 hom., cov: 31)

Consequence

NARS2
NM_024678.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.224
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NARS2NM_024678.6 linkuse as main transcriptc.1165-6648T>A intron_variant ENST00000281038.10 NP_078954.4 Q96I59-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NARS2ENST00000281038.10 linkuse as main transcriptc.1165-6648T>A intron_variant 1 NM_024678.6 ENSP00000281038.5 Q96I59-1

Frequencies

GnomAD3 genomes
AF:
0.225
AC:
34173
AN:
151910
Hom.:
4180
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.221
Gnomad AMI
AF:
0.176
Gnomad AMR
AF:
0.272
Gnomad ASJ
AF:
0.295
Gnomad EAS
AF:
0.414
Gnomad SAS
AF:
0.280
Gnomad FIN
AF:
0.290
Gnomad MID
AF:
0.269
Gnomad NFE
AF:
0.185
Gnomad OTH
AF:
0.233
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.225
AC:
34200
AN:
152028
Hom.:
4181
Cov.:
31
AF XY:
0.231
AC XY:
17171
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.221
Gnomad4 AMR
AF:
0.272
Gnomad4 ASJ
AF:
0.295
Gnomad4 EAS
AF:
0.415
Gnomad4 SAS
AF:
0.280
Gnomad4 FIN
AF:
0.290
Gnomad4 NFE
AF:
0.185
Gnomad4 OTH
AF:
0.231
Alfa
AF:
0.210
Hom.:
433
Bravo
AF:
0.224
Asia WGS
AF:
0.300
AC:
1040
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
7.2
DANN
Benign
0.83

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12287010; hg19: chr11-78161452; API