12-57512036-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_004990.4(MARS1):āc.1568T>Cā(p.Ile523Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I523V) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARS1 | NM_004990.4 | c.1568T>C | p.Ile523Thr | missense_variant | 13/21 | ENST00000262027.10 | |
MARS1 | XM_047428851.1 | c.866T>C | p.Ile289Thr | missense_variant | 9/17 | ||
MARS1 | XM_047428852.1 | c.1568T>C | p.Ile523Thr | missense_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARS1 | ENST00000262027.10 | c.1568T>C | p.Ile523Thr | missense_variant | 13/21 | 1 | NM_004990.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251444Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135906
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29AN XY: 727244
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74484
ClinVar
Submissions by phenotype
Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 08, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at