rs769544594
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004990.4(MARS1):c.1181G>A(p.Arg394His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R394C) has been classified 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARS1 | NM_004990.4 | c.1181G>A | p.Arg394His | missense_variant | 10/21 | ENST00000262027.10 | |
MARS1 | XM_047428851.1 | c.479G>A | p.Arg160His | missense_variant | 6/17 | ||
MARS1 | XM_047428852.1 | c.1181G>A | p.Arg394His | missense_variant | 10/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARS1 | ENST00000262027.10 | c.1181G>A | p.Arg394His | missense_variant | 10/21 | 1 | NM_004990.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000921 AC: 14AN: 152070Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251486Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135918
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727226
GnomAD4 genome ? AF: 0.0000921 AC: 14AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74270
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2023 | The c.1181G>A (p.R394H) alteration is located in exon 10 (coding exon 10) of the MARS gene. This alteration results from a G to A substitution at nucleotide position 1181, causing the arginine (R) at amino acid position 394 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, 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 | Invitae | May 18, 2023 | This variant has not been reported in the literature in individuals affected with MARS-related conditions. 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 542177). This variant is present in population databases (rs769544594, gnomAD 0.08%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 394 of the MARS protein (p.Arg394His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at