rs200279483
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_002047.4(GARS1):āc.408A>Gā(p.Gln136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 1,612,956 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).
Frequency
Genomes: š 0.00020 ( 0 hom., cov: 32)
Exomes š: 0.00040 ( 0 hom. )
Consequence
GARS1
NM_002047.4 synonymous
NM_002047.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.22
Genes affected
GARS1 (HGNC:4162): (glycyl-tRNA synthetase 1) This gene encodes glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids. The encoded enzyme is an (alpha)2 dimer which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 7-30600030-A-G is Benign according to our data. Variant chr7-30600030-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 385077.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=6, Uncertain_significance=1, Benign=1}.
BP7
?
Synonymous conserved (PhyloP=1.22 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000203 (31/152344) while in subpopulation NFE AF= 0.000382 (26/68032). AF 95% confidence interval is 0.000267. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GARS1 | NM_002047.4 | c.408A>G | p.Gln136= | synonymous_variant | 3/17 | ENST00000389266.8 | |
GARS1 | NM_001316772.1 | c.246A>G | p.Gln82= | synonymous_variant | 3/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GARS1 | ENST00000389266.8 | c.408A>G | p.Gln136= | synonymous_variant | 3/17 | 1 | NM_002047.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152226Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000112 AC: 28AN: 249552Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135390
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GnomAD4 exome AF: 0.000402 AC: 587AN: 1460612Hom.: 0 Cov.: 30 AF XY: 0.000402 AC XY: 292AN XY: 726738
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GnomAD4 genome ? AF: 0.000203 AC: 31AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74490
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:7
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 07, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2016 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 07, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | 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. - |
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
GARS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 19, 2019 | 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). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at