rs1085307775
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_005051.3(QARS1):c.1158C>T(p.Leu386Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005051.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.1158C>T | p.Leu386Leu | synonymous_variant | Exon 13 of 24 | ENST00000306125.12 | NP_005042.1 | |
QARS1 | NM_001272073.2 | c.1125C>T | p.Leu375Leu | synonymous_variant | Exon 13 of 24 | NP_001259002.1 | ||
QARS1 | XM_017006965.3 | c.1158C>T | p.Leu386Leu | synonymous_variant | Exon 13 of 23 | XP_016862454.2 | ||
QARS1 | NR_073590.2 | n.1133C>T | non_coding_transcript_exon_variant | Exon 13 of 24 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251012Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135644
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461884Hom.: 0 Cov.: 35 AF XY: 0.0000248 AC XY: 18AN XY: 727242
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1
The c.1158 C>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1158 C>T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is not conserved. Several in-silico splice prediction models predict that c.1158 C>T damaged the splice donor site for intron 6 which may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at