2-135907390-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001349.4(DARS1):āc.1432A>Cā(p.Met478Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,608,130 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 (ā ā ).
Frequency
Consequence
NM_001349.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DARS1 | NM_001349.4 | c.1432A>C | p.Met478Leu | missense_variant | Exon 16 of 16 | ENST00000264161.9 | NP_001340.2 | |
DARS1 | NM_001293312.1 | c.1132A>C | p.Met378Leu | 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.1432A>C | p.Met478Leu | missense_variant | Exon 16 of 16 | 1 | NM_001349.4 | ENSP00000264161.4 | ||
DARS1 | ENST00000422708.3 | c.493A>C | p.Met165Leu | missense_variant | Exon 6 of 6 | 2 | ENSP00000387508.1 | |||
DARS1 | ENST00000478212.5 | n.326A>C | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | |||||
DARS1 | ENST00000489964.5 | n.681A>C | non_coding_transcript_exon_variant | Exon 5 of 5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151866Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248284Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134512
GnomAD4 exome AF: 0.00000412 AC: 6AN: 1456264Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3AN XY: 724656
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151866Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2AN XY: 74190
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1432A>C (p.M478L) alteration is located in exon 16 (coding exon 16) of the DARS gene. This alteration results from a A to C substitution at nucleotide position 1432, causing the methionine (M) at amino acid position 478 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at