rs587776688
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_005548.3(KARS1):c.431_432insTT(p.Tyr145SerfsTer9) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
KARS1
NM_005548.3 frameshift
NM_005548.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.06
Genes affected
KARS1 (HGNC:6215): (lysyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 16-75636504-G-GAA is Pathogenic according to our data. Variant chr16-75636504-G-GAA is described in ClinVar as [Pathogenic]. Clinvar id is 8170.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KARS1 | NM_005548.3 | c.431_432insTT | p.Tyr145SerfsTer9 | frameshift_variant | 4/14 | ENST00000302445.8 | |
KARS1 | NM_001130089.2 | c.515_516insTT | p.Tyr173SerfsTer9 | frameshift_variant | 5/15 | ||
KARS1 | NM_001378148.1 | c.-38_-37insTT | 5_prime_UTR_variant | 4/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KARS1 | ENST00000302445.8 | c.431_432insTT | p.Tyr145SerfsTer9 | frameshift_variant | 4/14 | 1 | NM_005548.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease recessive intermediate B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 08, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at