rs777424712
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005051.3(QARS1):āc.1163A>Gā(p.Glu388Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. 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. E388D) has been classified as Uncertain significance.
Frequency
Consequence
NM_005051.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.1163A>G | p.Glu388Gly | missense_variant, splice_region_variant | 13/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.1130A>G | p.Glu377Gly | missense_variant, splice_region_variant | 13/24 | ||
QARS1 | XM_017006965.3 | c.1163A>G | p.Glu388Gly | missense_variant, splice_region_variant | 13/23 | ||
QARS1 | NR_073590.2 | n.1138A>G | splice_region_variant, non_coding_transcript_exon_variant | 13/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.1163A>G | p.Glu388Gly | missense_variant, splice_region_variant | 13/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251044Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135654
GnomAD4 exome AF: 0.0000766 AC: 112AN: 1461884Hom.: 0 Cov.: 35 AF XY: 0.0000674 AC XY: 49AN XY: 727240
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74348
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 | Oct 17, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 388 of the QARS protein (p.Glu388Gly). This variant is present in population databases (rs777424712, gnomAD 0.003%). 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: 567795). 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: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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