rs142327602
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_005051.3(QARS1):c.2123C>T(p.Pro708Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,614,152 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P708A) has been classified as Uncertain significance.
Frequency
Consequence
NM_005051.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
QARS1 | NM_005051.3 | c.2123C>T | p.Pro708Leu | missense_variant | 22/24 | ENST00000306125.12 | |
QARS1 | NM_001272073.2 | c.2090C>T | p.Pro697Leu | missense_variant | 22/24 | ||
QARS1 | XM_017006965.3 | c.2123C>T | p.Pro708Leu | missense_variant | 22/23 | ||
QARS1 | NR_073590.2 | n.2098C>T | non_coding_transcript_exon_variant | 22/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
QARS1 | ENST00000306125.12 | c.2123C>T | p.Pro708Leu | missense_variant | 22/24 | 1 | NM_005051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000973 AC: 148AN: 152146Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000255 AC: 64AN: 251458Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135908
GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000633 AC XY: 46AN XY: 727244
GnomAD4 genome ? AF: 0.000985 AC: 150AN: 152264Hom.: 0 Cov.: 31 AF XY: 0.000967 AC XY: 72AN XY: 74462
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Oct 28, 2022 | This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.3% (142/41414) (https://gnomad.broadinstitute.org/variant/3-49098220-G-A?dataset=gnomad_r3). This variant is present in ClinVar, with multiple labs classifying this variant as Likely Benign (Variation ID:477838). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 10, 2023 | BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2023 | 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; This variant is associated with the following publications: (PMID: 25471517) - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
QARS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 20, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at