rs1396171148
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_005687.5(FARSB):c.1381A>C(p.Thr461Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
FARSB
NM_005687.5 missense
NM_005687.5 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 7.53
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 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.906
PP5
Variant 2-222613892-T-G is Pathogenic according to our data. Variant chr2-222613892-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 545642.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FARSB | NM_005687.5 | c.1381A>C | p.Thr461Pro | missense_variant | 15/17 | ENST00000281828.8 | NP_005678.3 | |
FARSB | XM_006712169.3 | c.1084A>C | p.Thr362Pro | missense_variant | 16/18 | XP_006712232.1 | ||
FARSB | XM_011510466.3 | c.1084A>C | p.Thr362Pro | missense_variant | 16/18 | XP_011508768.1 | ||
FARSB | NR_130154.2 | n.1596A>C | non_coding_transcript_exon_variant | 16/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FARSB | ENST00000281828.8 | c.1381A>C | p.Thr461Pro | missense_variant | 15/17 | 1 | NM_005687.5 | ENSP00000281828.6 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Vascular dilatation;C0023890:Cirrhosis of liver;C0206061:Interstitial pneumonitis;C0270685:Cerebral calcification Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | May 28, 2018 | - - |
Rajab interstitial lung disease with brain calcifications Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 08, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of stability (P = 0.2406);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at