rs1064797070
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005051.3(QARS1):c.1418C>T(p.Ala473Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A473P) 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.1418C>T | p.Ala473Val | missense_variant | 16/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.1385C>T | p.Ala462Val | missense_variant | 16/24 | ||
QARS1 | XM_017006965.3 | c.1418C>T | p.Ala473Val | missense_variant | 16/23 | ||
QARS1 | NR_073590.2 | n.1393C>T | non_coding_transcript_exon_variant | 16/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.1418C>T | p.Ala473Val | missense_variant | 16/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251354Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135836
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461814Hom.: 0 Cov.: 35 AF XY: 0.0000179 AC XY: 13AN XY: 727202
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2021 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Unavailable"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with QARS-related disease. ClinVar contains an entry for this variant (Variation ID: 424612). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 473 of the QARS protein (p.Ala473Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at