3-49098054-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005051.3(QARS1):c.2215G>A(p.Asp739Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,614,006 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D739Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_005051.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.2215G>A | p.Asp739Asn | missense_variant | 23/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.2182G>A | p.Asp728Asn | missense_variant | 23/24 | ||
QARS1 | XM_017006965.3 | c.2151+138G>A | intron_variant | ||||
QARS1 | NR_073590.2 | n.2190G>A | non_coding_transcript_exon_variant | 23/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.2215G>A | p.Asp739Asn | missense_variant | 23/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152126Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251490Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135916
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727236
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152126Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74318
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; 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 | Sep 27, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 739 of the QARS protein (p.Asp739Asn). This variant is present in population databases (rs749055007, gnomAD 0.004%). 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: 857235). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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