rs1135401747
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_002047.4(GARS1):c.246_249delAGAA(p.Glu83fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GARS1
NM_002047.4 frameshift
NM_002047.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.67
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 Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-30598816-CAAAG-C is Pathogenic according to our data. Variant chr7-30598816-CAAAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 431180.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GARS1 | NM_002047.4 | c.246_249delAGAA | p.Glu83fs | frameshift_variant | 2/17 | ENST00000389266.8 | NP_002038.2 | |
| GARS1 | NM_001316772.1 | c.84_87delAGAA | p.Glu29fs | frameshift_variant | 2/17 | NP_001303701.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GARS1 | ENST00000389266.8 | c.246_249delAGAA | p.Glu83fs | frameshift_variant | 2/17 | 1 | NM_002047.4 | ENSP00000373918.3 | ||
| GARS1 | ENST00000675651.1 | c.246_249delAGAA | p.Glu83fs | frameshift_variant | 2/17 | ENSP00000502513.1 | ||||
| GARS1 | ENST00000675693.1 | c.78_81delAGAA | p.Glu27fs | frameshift_variant | 3/18 | ENSP00000502174.1 | ||||
| GARS1 | ENST00000675051.1 | c.45_48delAGAA | p.Glu16fs | frameshift_variant | 2/17 | ENSP00000502296.1 | ||||
| GARS1 | ENST00000674815 | c.-124_-121delAGAA | 5_prime_UTR_variant | 2/17 | ENSP00000502799.1 | |||||
| GARS1 | ENST00000674851 | c.-124_-121delAGAA | 5_prime_UTR_variant | 3/18 | ENSP00000502451.1 | |||||
| GARS1 | ENST00000675810.1 | c.223-1128_223-1125delAGAA | intron_variant | ENSP00000502743.1 | ||||||
| GARS1 | ENST00000444666.6 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/18 | 3 | ENSP00000415447.2 | ||||
| GARS1 | ENST00000674616.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/18 | ENSP00000502408.1 | |||||
| GARS1 | ENST00000674643.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/17 | ENSP00000501636.1 | |||||
| GARS1 | ENST00000674737.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/18 | ENSP00000502464.1 | |||||
| GARS1 | ENST00000674807.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/16 | ENSP00000502814.1 | |||||
| GARS1 | ENST00000675529.1 | n.*116_*119delAGAA | non_coding_transcript_exon_variant | 3/18 | ENSP00000501655.1 | |||||
| GARS1 | ENST00000675859.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/15 | ENSP00000502033.1 | |||||
| GARS1 | ENST00000676088.1 | n.*116_*119delAGAA | non_coding_transcript_exon_variant | 3/19 | ENSP00000501884.1 | |||||
| GARS1 | ENST00000676140.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/17 | ENSP00000502571.1 | |||||
| GARS1 | ENST00000676164.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/17 | ENSP00000501986.1 | |||||
| GARS1 | ENST00000676210.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/18 | ENSP00000502373.1 | |||||
| GARS1 | ENST00000676259.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/17 | ENSP00000501980.1 | |||||
| GARS1 | ENST00000676403.1 | n.246_249delAGAA | non_coding_transcript_exon_variant | 2/16 | ENSP00000502681.1 | |||||
| GARS1 | ENST00000675529.1 | n.*116_*119delAGAA | 3_prime_UTR_variant | 3/18 | ENSP00000501655.1 | |||||
| GARS1 | ENST00000676088.1 | n.*116_*119delAGAA | 3_prime_UTR_variant | 3/19 | ENSP00000501884.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461740Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727192
GnomAD4 exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
GARS-associated growth retardation and developmental delay Pathogenic:1
| Pathogenic, no assertion criteria provided | clinical testing;research | Antonellis Laboratory at Michigan, University of Michigan | - | This variant is associated with a recessive, multi-system disorder described in PMID: 28675565. - |
Computational scores
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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