chr5-168486501-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 12P and 4B. PVS1PS1_ModeratePP5_ModerateBS2
The NM_002887.4(RARS1):c.3G>T(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000122 in 1,558,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
RARS1
NM_002887.4 start_lost
NM_002887.4 start_lost
Scores
5
7
4
Clinical Significance
Conservation
PhyloP100: 5.70
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_002887.4 (RARS1) was described as [Likely_pathogenic] in ClinVar as 391980
PP5
?
Variant 5-168486501-G-T is Pathogenic according to our data. Variant chr5-168486501-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 1218728.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RARS1 | NM_002887.4 | c.3G>T | p.Met1? | start_lost | 1/15 | ENST00000231572.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RARS1 | ENST00000231572.8 | c.3G>T | p.Met1? | start_lost | 1/15 | 1 | NM_002887.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152196Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000995 AC: 14AN: 1406486Hom.: 0 Cov.: 30 AF XY: 0.00000720 AC XY: 5AN XY: 694164
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2022 | Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31814314) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Pathogenic
D;.
Sift4G
Uncertain
T;D
Polyphen
P;.
Vest4
MutPred
Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at