rs758523839
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_004990.4(MARS1):āc.920A>Gā(p.Tyr307Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,614,002 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 Likely pathogenic (no stars).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
MARS1
NM_004990.4 missense
NM_004990.4 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 4.48
Genes affected
MARS1 (HGNC:6898): (methionyl-tRNA synthetase 1) This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. The encoded protein is a component of the multi-tRNA synthetase complex and catalyzes the ligation of methionine to tRNA molecules. [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.924
PP5
?
Variant 12-57498452-A-G is Pathogenic according to our data. Variant chr12-57498452-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 496635.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-57498452-A-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARS1 | NM_004990.4 | c.920A>G | p.Tyr307Cys | missense_variant | 9/21 | ENST00000262027.10 | |
MARS1 | XM_047428851.1 | c.218A>G | p.Tyr73Cys | missense_variant | 5/17 | ||
MARS1 | XM_047428852.1 | c.920A>G | p.Tyr307Cys | missense_variant | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARS1 | ENST00000262027.10 | c.920A>G | p.Tyr307Cys | missense_variant | 9/21 | 1 | NM_004990.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251470Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135910
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727216
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74324
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Hadassah Hebrew University Medical Center | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at T311 (P = 2e-04);
MVP
MPC
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