rs753793246
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_001349.4(DARS1):āc.1460G>Cā(p.Arg487Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R487C) has been classified as Pathogenic.
Frequency
Consequence
NM_001349.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DARS1 | NM_001349.4 | c.1460G>C | p.Arg487Pro | missense_variant | Exon 16 of 16 | ENST00000264161.9 | NP_001340.2 | |
DARS1 | NM_001293312.1 | c.1160G>C | p.Arg387Pro | missense_variant | Exon 15 of 15 | NP_001280241.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DARS1 | ENST00000264161.9 | c.1460G>C | p.Arg487Pro | missense_variant | Exon 16 of 16 | 1 | NM_001349.4 | ENSP00000264161.4 | ||
DARS1 | ENST00000422708.3 | c.521G>C | p.Arg174Pro | missense_variant | Exon 6 of 6 | 2 | ENSP00000387508.1 | |||
DARS1 | ENST00000478212.5 | n.354G>C | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | |||||
DARS1 | ENST00000489964.5 | n.709G>C | non_coding_transcript_exon_variant | Exon 5 of 5 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249204Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134914
GnomAD4 exome AF: 0.00000275 AC: 4AN: 1452528Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 722742
GnomAD4 genome Cov.: 31
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at