rs201597392
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004990.4(MARS1):c.699T>G(p.Ile233Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARS1 | NM_004990.4 | c.699T>G | p.Ile233Met | missense_variant | 7/21 | ENST00000262027.10 | |
MARS1 | XM_047428852.1 | c.699T>G | p.Ile233Met | missense_variant | 7/15 | ||
MARS1 | XM_047428851.1 | c.-4T>G | 5_prime_UTR_variant | 3/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARS1 | ENST00000262027.10 | c.699T>G | p.Ile233Met | missense_variant | 7/21 | 1 | NM_004990.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152134Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251496Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135922
GnomAD4 exome AF: 0.0000951 AC: 139AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000990 AC XY: 72AN XY: 727244
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152252Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 4AN XY: 74450
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
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 | Invitae | Dec 14, 2023 | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 233 of the MARS protein (p.Ile233Met). This variant is present in population databases (rs201597392, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical suspicion of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 449718). 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 | clinical testing | GeneDx | Oct 23, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at