12-57498433-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP4_StrongBP6_Very_StrongBS2
The NM_004990.4(MARS1):c.901C>T(p.Arg301Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000421 in 1,613,726 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R301H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004990.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARS1 | NM_004990.4 | c.901C>T | p.Arg301Cys | missense_variant | 9/21 | ENST00000262027.10 | |
MARS1 | XM_047428851.1 | c.199C>T | p.Arg67Cys | missense_variant | 5/17 | ||
MARS1 | XM_047428852.1 | c.901C>T | p.Arg301Cys | missense_variant | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARS1 | ENST00000262027.10 | c.901C>T | p.Arg301Cys | missense_variant | 9/21 | 1 | NM_004990.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000519 AC: 79AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000831 AC: 209AN: 251384Hom.: 2 AF XY: 0.000927 AC XY: 126AN XY: 135860
GnomAD4 exome AF: 0.000411 AC: 600AN: 1461586Hom.: 6 Cov.: 32 AF XY: 0.000466 AC XY: 339AN XY: 727084
GnomAD4 genome ? AF: 0.000519 AC: 79AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.000404 AC XY: 30AN XY: 74334
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 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 | Invitae | Jan 22, 2024 | - - |
MARS1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 24, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at