2-135907329-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001349.4(DARS1):c.1493G>A(p.Arg498Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000703 in 1,563,788 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 Uncertain significance (★★).
Frequency
Consequence
NM_001349.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DARS1 | NM_001349.4 | c.1493G>A | p.Arg498Gln | missense_variant | Exon 16 of 16 | ENST00000264161.9 | NP_001340.2 | |
DARS1 | NM_001293312.1 | c.1193G>A | p.Arg398Gln | 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.1493G>A | p.Arg498Gln | missense_variant | Exon 16 of 16 | 1 | NM_001349.4 | ENSP00000264161.4 | ||
DARS1 | ENST00000422708.3 | c.554G>A | p.Arg185Gln | missense_variant | Exon 6 of 6 | 2 | ENSP00000387508.1 | |||
DARS1 | ENST00000478212.5 | n.387G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | |||||
DARS1 | ENST00000489964.5 | n.742G>A | non_coding_transcript_exon_variant | Exon 5 of 5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000279 AC: 4AN: 143374Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248726Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134714
GnomAD4 exome AF: 0.00000493 AC: 7AN: 1420414Hom.: 0 Cov.: 30 AF XY: 0.00000283 AC XY: 2AN XY: 706564
GnomAD4 genome AF: 0.0000279 AC: 4AN: 143374Hom.: 0 Cov.: 30 AF XY: 0.0000434 AC XY: 3AN XY: 69102
ClinVar
Submissions by phenotype
Hypomyelination with brain stem and spinal cord involvement and leg spasticity Uncertain:1
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Inborn genetic diseases Uncertain:1
The c.1493G>A (p.R498Q) alteration is located in exon 16 (coding exon 16) of the DARS gene. This alteration results from a G to A substitution at nucleotide position 1493, causing the arginine (R) at amino acid position 498 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at