rs1553123307
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_003680.4(YARS1):c.739_740delinsGC(p.Lys247Ala) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
YARS1
NM_003680.4 missense
NM_003680.4 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.61
Genes affected
YARS1 (HGNC:12840): (tyrosyl-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. Tyrosyl-tRNA synthetase belongs to the class I tRNA synthetase family. Cytokine activities have also been observed for the human tyrosyl-tRNA synthetase, after it is split into two parts, an N-terminal fragment that harbors the catalytic site and a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
YARS1 | NM_003680.4 | c.739_740delinsGC | p.Lys247Ala | missense_variant | 7/13 | ENST00000373477.9 | |
YARS1 | XM_011542347.3 | c.109_110delinsGC | p.Lys37Ala | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
YARS1 | ENST00000373477.9 | c.739_740delinsGC | p.Lys247Ala | missense_variant | 7/13 | 1 | NM_003680.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease dominant intermediate C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 15, 2023 | ClinVar contains an entry for this variant (Variation ID: 464879). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces lysine, which is basic and polar, with alanine, which is neutral and non-polar, at codon 247 of the YARS protein (p.Lys247Ala). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with YARS-related conditions. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at