rs754360926
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_002047.4(GARS1):c.144C>T(p.Ala48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,550,616 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
GARS1
NM_002047.4 synonymous
NM_002047.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.586
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 7-30595065-C-T is Benign according to our data. Variant chr7-30595065-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 585899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.586 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000328 (5/152220) while in subpopulation EAS AF= 0.000771 (4/5188). AF 95% confidence interval is 0.000263. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GARS1 | NM_002047.4 | c.144C>T | p.Ala48= | synonymous_variant | 1/17 | ENST00000389266.8 | |
GARS1 | NM_001316772.1 | c.-19C>T | 5_prime_UTR_variant | 1/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GARS1 | ENST00000389266.8 | c.144C>T | p.Ala48= | synonymous_variant | 1/17 | 1 | NM_002047.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000980 AC: 15AN: 153122Hom.: 0 AF XY: 0.000108 AC XY: 9AN XY: 83706
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GnomAD4 exome AF: 0.0000186 AC: 26AN: 1398396Hom.: 0 Cov.: 36 AF XY: 0.0000130 AC XY: 9AN XY: 691628
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74358
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
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 type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 21, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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