rs750907390
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005051.3(QARS1):āc.1738A>Gā(p.Thr580Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T580I) has been classified as Uncertain significance.
Frequency
Consequence
NM_005051.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.1738A>G | p.Thr580Ala | missense_variant | 18/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.1705A>G | p.Thr569Ala | missense_variant | 18/24 | ||
QARS1 | XM_017006965.3 | c.1738A>G | p.Thr580Ala | missense_variant | 18/23 | ||
QARS1 | NR_073590.2 | n.1713A>G | non_coding_transcript_exon_variant | 18/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.1738A>G | p.Thr580Ala | missense_variant | 18/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152078Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251398Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135860
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461884Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727240
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74280
ClinVar
Submissions by phenotype
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 580 of the QARS protein (p.Thr580Ala). This variant is present in population databases (rs750907390, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with QARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 578717). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at