chr7-30594884-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002047.4(GARS1):c.-38G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 1,501,554 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
GARS1
NM_002047.4 5_prime_UTR
NM_002047.4 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.304
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GARS1 | NM_002047.4 | c.-38G>A | 5_prime_UTR_variant | 1/17 | ENST00000389266.8 | ||
GARS1 | NM_001316772.1 | c.-200G>A | 5_prime_UTR_variant | 1/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GARS1 | ENST00000389266.8 | c.-38G>A | 5_prime_UTR_variant | 1/17 | 1 | NM_002047.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000163 AC: 22AN: 1349278Hom.: 0 Cov.: 25 AF XY: 0.0000135 AC XY: 9AN XY: 667586
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74466
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2017 | The c.-38 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.-38 G>A variant is not observed in large population cohorts (1000 Genomes Consortium et al., 2015; Exome Variant Server) This variant is not in the Kozak consensus sequence, which plays a role in the initiation of protein translation. This substitution occurs at a position that is conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at