12-57516258-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004990.4(MARS1):c.2477C>T(p.Pro826Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004990.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MARS1 | NM_004990.4 | c.2477C>T | p.Pro826Leu | missense_variant | 20/21 | ENST00000262027.10 | NP_004981.2 | |
MARS1 | XM_047428851.1 | c.1775C>T | p.Pro592Leu | missense_variant | 16/17 | XP_047284807.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MARS1 | ENST00000262027.10 | c.2477C>T | p.Pro826Leu | missense_variant | 20/21 | 1 | NM_004990.4 | ENSP00000262027 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251478Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135914
GnomAD4 exome AF: 0.0000835 AC: 122AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000798 AC XY: 58AN XY: 727240
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74282
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 09, 2022 | The p.P826L variant (also known as c.2477C>T), located in coding exon 20 of the MARS gene, results from a C to T substitution at nucleotide position 2477. The proline at codon 826 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Charcot-Marie-Tooth disease axonal type 2U;C4225400:Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 20, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 826 of the MARS protein (p.Pro826Leu). This variant is present in population databases (rs138343927, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 570331). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at