rs1312438512

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePS1_ModeratePM2

The NM_002887.4(RARS1):​c.3G>A​(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000000711 in 1,406,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RARS1
NM_002887.4 start_lost

Scores

5
7
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.70
Variant links:
Genes affected
RARS1 (HGNC:9870): (arginyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Arginyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 216 CDS bases. Genomic position: 168492694. Lost 0.109 part of the original CDS.
PS1
Another start lost variant in NM_002887.4 (RARS1) was described as [Pathogenic] in Lovd
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RARS1NM_002887.4 linkc.3G>A p.Met1? start_lost Exon 1 of 15 ENST00000231572.8 NP_002878.2 P54136-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RARS1ENST00000231572.8 linkc.3G>A p.Met1? start_lost Exon 1 of 15 1 NM_002887.4 ENSP00000231572.3 P54136-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.11e-7
AC:
1
AN:
1406490
Hom.:
0
Cov.:
30
AF XY:
0.00000144
AC XY:
1
AN XY:
694166
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.24e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.24
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Pathogenic
0.62
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Benign
-0.31
T
PROVEAN
Benign
-0.68
N;.
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.056
T;D
Polyphen
0.85
P;.
Vest4
0.85
MutPred
1.0
Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP
0.79
ClinPred
1.0
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.94
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs1312438512; hg19: chr5-167913506; API