rs151260441
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1
The NM_004990.4(MARS1):c.801C>T(p.Leu267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
MARS1
NM_004990.4 synonymous
NM_004990.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0700
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 Benign. Variant got -13 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 12-57498187-C-T is Benign according to our data. Variant chr12-57498187-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 475431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.07 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00126 (192/152328) while in subpopulation AFR AF= 0.00428 (178/41580). AF 95% confidence interval is 0.00377. There are 0 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MARS1 | NM_004990.4 | c.801C>T | p.Leu267= | synonymous_variant | 8/21 | ENST00000262027.10 | NP_004981.2 | |
MARS1 | XM_047428851.1 | c.99C>T | p.Leu33= | synonymous_variant | 4/17 | XP_047284807.1 | ||
MARS1 | XM_047428852.1 | c.801C>T | p.Leu267= | synonymous_variant | 8/15 | XP_047284808.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MARS1 | ENST00000262027.10 | c.801C>T | p.Leu267= | synonymous_variant | 8/21 | 1 | NM_004990.4 | ENSP00000262027 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00126 AC: 192AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000342 AC: 86AN: 251480Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135916
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GnomAD4 exome AF: 0.000132 AC: 193AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.000143 AC XY: 104AN XY: 727204
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GnomAD4 genome AF: 0.00126 AC: 192AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.00121 AC XY: 90AN XY: 74502
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 23, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease axonal type 2U;C4225400:Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 05, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at