rs369152939
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_001349.4(DARS1):c.821C>T(p.Ala274Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,598,230 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. A274G) 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 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DARS1 | NM_001349.4 | c.821C>T | p.Ala274Val | missense_variant | 10/16 | ENST00000264161.9 | |
DARS1 | NM_001293312.1 | c.521C>T | p.Ala174Val | missense_variant | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DARS1 | ENST00000264161.9 | c.821C>T | p.Ala274Val | missense_variant | 10/16 | 1 | NM_001349.4 | P1 | |
DARS1 | ENST00000422708.3 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152030Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1446200Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2AN XY: 719038
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152030Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74266
ClinVar
Submissions by phenotype
Hypomyelination with brain stem and spinal cord involvement and leg spasticity Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 02, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at