rs1553549333
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_005687.5(FARSB):c.1486delinsAA(p.His496LysfsTer14) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
FARSB
NM_005687.5 frameshift
NM_005687.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.81
Genes affected
FARSB (HGNC:17800): (phenylalanyl-tRNA synthetase subunit beta) This gene encodes a highly conserved enzyme that belongs to the aminoacyl-tRNA synthetase class IIc subfamily. This enzyme comprises the regulatory beta subunits that form a tetramer with two catalytic alpha subunits. In the presence of ATP, this tetramer is responsible for attaching L-phenylalanine to the terminal adenosine of the appropriate tRNA. A pseudogene located on chromosome 10 has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.16 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-222600060-G-TT is Pathogenic according to our data. Variant chr2-222600060-G-TT is described in ClinVar as [Pathogenic]. Clinvar id is 487456.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FARSB | NM_005687.5 | c.1486delinsAA | p.His496LysfsTer14 | frameshift_variant | 16/17 | ENST00000281828.8 | |
FARSB | XM_006712169.3 | c.1189delinsAA | p.His397LysfsTer14 | frameshift_variant | 17/18 | ||
FARSB | XM_011510466.3 | c.1189delinsAA | p.His397LysfsTer14 | frameshift_variant | 17/18 | ||
FARSB | NR_130154.2 | n.1701delinsAA | non_coding_transcript_exon_variant | 17/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FARSB | ENST00000281828.8 | c.1486delinsAA | p.His496LysfsTer14 | frameshift_variant | 16/17 | 1 | NM_005687.5 | P1 |
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:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rajab interstitial lung disease with brain calcifications Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 08, 2020 | - - |
Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency Pathogenic:1
Likely pathogenic, no assertion criteria provided | in vitro | Antonellis Laboratory at Michigan, University of Michigan | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 24, 2018 | The c.1486delCinsAA variant in the FARSB gene has been published in association with FARSB-related disorders (Antonellis et al., 2018). The c.1486delCinsAA variant causes a frameshift starting with codon Histidine 496, changes this amino acid to a Lysine residue and creates a premature Stop codon at position 14 of the new reading frame, denoted p.His496LysfsX14. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1486delCinsAA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1486delCinsAA as a pathogenic variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at