rs137973249

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001083614.2(EARS2):ā€‹c.1412A>Gā€‹(p.Lys471Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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 š‘“: 0.0000089 ( 0 hom. )

Consequence

EARS2
NM_001083614.2 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.202
Variant links:
Genes affected
EARS2 (HGNC:29419): (glutamyl-tRNA synthetase 2, mitochondrial) This gene encodes a member of the class I 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 glutamate to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 12 (COXPD12). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11442441).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EARS2NM_001083614.2 linkc.1412A>G p.Lys471Arg missense_variant 8/9 ENST00000449606.7 NP_001077083.1 Q5JPH6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EARS2ENST00000449606.7 linkc.1412A>G p.Lys471Arg missense_variant 8/91 NM_001083614.2 ENSP00000395196.2 Q5JPH6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
249494
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135374
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461874
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.11
T;T;T;.
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.68
T;.;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.0
M;M;.;M
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.85
N;N;N;N
REVEL
Benign
0.085
Sift
Benign
0.24
T;T;T;T
Sift4G
Benign
0.42
T;T;T;T
Polyphen
0.0020
B;B;.;.
Vest4
0.077
MutPred
0.26
Loss of ubiquitination at K471 (P = 0.0141);Loss of ubiquitination at K471 (P = 0.0141);Loss of ubiquitination at K471 (P = 0.0141);Loss of ubiquitination at K471 (P = 0.0141);
MVP
0.57
MPC
0.14
ClinPred
0.075
T
GERP RS
2.9
Varity_R
0.033
gMVP
0.17

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: rs137973249; hg19: chr16-23536641; API