11-78568744-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024678.6(NARS2):c.260A>C(p.Asn87Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,602,524 control chromosomes in the GnomAD database, including 485,488 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44245 hom., cov: 32)

Exomes 𝑓: 0.78 ( 441243 hom. )

Consequence

NARS2
NM_024678.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.90

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]

NARS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.725515E-7).

BP6

Variant 11-78568744-T-G is Benign according to our data. Variant chr11-78568744-T-G is described in ClinVar as [Benign]. Clinvar id is 380000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NARS2	NM_024678.6 link	c.260A>C	p.Asn87Thr	missense_variant	Exon 3 of 14	ENST00000281038.10	NP_078954.4	Q96I59-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NARS2	ENST00000281038.10 link	c.260A>C	p.Asn87Thr	missense_variant	Exon 3 of 14	1	NM_024678.6	ENSP00000281038.5		Q96I59-1

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115489

AN:

151892

Hom.:

44212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.796

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.740

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.684

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.795

Gnomad OTH

AF:

0.756

GnomAD3 exomes

AF:

0.727

AC:

181662

AN:

249758

Hom.:

67021

AF XY:

0.733

AC XY:

99009

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.774

Gnomad AMR exome

AF:

0.584

Gnomad ASJ exome

AF:

0.740

Gnomad EAS exome

AF:

0.585

Gnomad SAS exome

AF:

0.713

Gnomad FIN exome

AF:

0.699

Gnomad NFE exome

AF:

0.793

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.778

AC:

1127921

AN:

1450514

Hom.:

441243

Cov.:

AF XY:

0.777

AC XY:

560760

AN XY:

722062

show subpopulations

Gnomad4 AFR exome

AF:

0.777

Gnomad4 AMR exome

AF:

0.593

Gnomad4 ASJ exome

AF:

0.737

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.707

Gnomad4 FIN exome

AF:

0.709

Gnomad4 NFE exome

AF:

0.802

Gnomad4 OTH exome

AF:

0.762

GnomAD4 genome

AF:

0.760

AC:

115576

AN:

152010

Hom.:

44245

Cov.:

AF XY:

0.753

AC XY:

55994

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.687

Gnomad4 ASJ

AF:

0.740

Gnomad4 EAS

AF:

0.588

Gnomad4 SAS

AF:

0.723

Gnomad4 FIN

AF:

0.684

Gnomad4 NFE

AF:

0.795

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.783

Hom.:

109383

Bravo

AF:

0.757

TwinsUK

AF:

0.803

AC:

2976

ALSPAC

AF:

0.807

AC:

3111

ESP6500AA

AF:

0.780

AC:

3430

ESP6500EA

AF:

0.796

AC:

6835

ExAC

AF:

0.738

AC:

89583

Asia WGS

AF:

0.701

AC:

2436

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation defect type 24

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 02, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hearing loss, autosomal recessive 94

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.9

DANN

Benign

0.40

DEOGEN2

Benign

0.0085

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.0070

T;T

MetaRNN

Benign

8.7e-7

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.9

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.077

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;.

Vest4

0.025

MPC

0.046

ClinPred

0.0016

GERP RS

4.5

Varity_R

0.052

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over