7-30632320-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_002047.4(GARS1):c.1977C>T(p.Ala659Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
GARS1
NM_002047.4 synonymous
NM_002047.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.66
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 -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 7-30632320-C-T is Benign according to our data. Variant chr7-30632320-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 476754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.65 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GARS1 | NM_002047.4 | c.1977C>T | p.Ala659Ala | synonymous_variant | 16/17 | ENST00000389266.8 | NP_002038.2 | |
| GARS1 | NM_001316772.1 | c.1815C>T | p.Ala605Ala | synonymous_variant | 16/17 | NP_001303701.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GARS1 | ENST00000389266.8 | c.1977C>T | p.Ala659Ala | synonymous_variant | 16/17 | 1 | NM_002047.4 | ENSP00000373918.3 | ||
| GARS1 | ENST00000675651.1 | c.1995C>T | p.Ala665Ala | synonymous_variant | 16/17 | ENSP00000502513.1 | ||||
| GARS1 | ENST00000675810.1 | c.1875C>T | p.Ala625Ala | synonymous_variant | 15/16 | ENSP00000502743.1 | ||||
| GARS1 | ENST00000675693.1 | c.1809C>T | p.Ala603Ala | synonymous_variant | 17/18 | ENSP00000502174.1 | ||||
| GARS1 | ENST00000675051.1 | c.1776C>T | p.Ala592Ala | synonymous_variant | 16/17 | ENSP00000502296.1 | ||||
| GARS1 | ENST00000674815.1 | c.1608C>T | p.Ala536Ala | synonymous_variant | 16/17 | ENSP00000502799.1 | ||||
| GARS1 | ENST00000674851.1 | c.1608C>T | p.Ala536Ala | synonymous_variant | 17/18 | ENSP00000502451.1 | ||||
| GARS1 | ENST00000444666.6 | n.*398C>T | non_coding_transcript_exon_variant | 17/18 | 3 | ENSP00000415447.2 | ||||
| GARS1 | ENST00000674616.1 | n.*1691C>T | non_coding_transcript_exon_variant | 17/18 | ENSP00000502408.1 | |||||
| GARS1 | ENST00000674643.1 | n.*1782C>T | non_coding_transcript_exon_variant | 16/17 | ENSP00000501636.1 | |||||
| GARS1 | ENST00000674737.1 | n.*1315C>T | non_coding_transcript_exon_variant | 17/18 | ENSP00000502464.1 | |||||
| GARS1 | ENST00000674807.1 | n.*250C>T | non_coding_transcript_exon_variant | 15/16 | ENSP00000502814.1 | |||||
| GARS1 | ENST00000675529.1 | n.*1847C>T | non_coding_transcript_exon_variant | 17/18 | ENSP00000501655.1 | |||||
| GARS1 | ENST00000675859.1 | n.*156C>T | non_coding_transcript_exon_variant | 14/15 | ENSP00000502033.1 | |||||
| GARS1 | ENST00000676088.1 | n.*1919C>T | non_coding_transcript_exon_variant | 18/19 | ENSP00000501884.1 | |||||
| GARS1 | ENST00000676140.1 | n.*922C>T | non_coding_transcript_exon_variant | 16/17 | ENSP00000502571.1 | |||||
| GARS1 | ENST00000676164.1 | n.*1428C>T | non_coding_transcript_exon_variant | 16/17 | ENSP00000501986.1 | |||||
| GARS1 | ENST00000676210.1 | n.*1266C>T | non_coding_transcript_exon_variant | 17/18 | ENSP00000502373.1 | |||||
| GARS1 | ENST00000676259.1 | n.*1409C>T | non_coding_transcript_exon_variant | 16/17 | ENSP00000501980.1 | |||||
| GARS1 | ENST00000676403.1 | n.*62C>T | non_coding_transcript_exon_variant | 15/16 | ENSP00000502681.1 | |||||
| GARS1 | ENST00000444666.6 | n.*398C>T | 3_prime_UTR_variant | 17/18 | 3 | ENSP00000415447.2 | ||||
| GARS1 | ENST00000674616.1 | n.*1691C>T | 3_prime_UTR_variant | 17/18 | ENSP00000502408.1 | |||||
| GARS1 | ENST00000674643.1 | n.*1782C>T | 3_prime_UTR_variant | 16/17 | ENSP00000501636.1 | |||||
| GARS1 | ENST00000674737.1 | n.*1315C>T | 3_prime_UTR_variant | 17/18 | ENSP00000502464.1 | |||||
| GARS1 | ENST00000674807.1 | n.*250C>T | 3_prime_UTR_variant | 15/16 | ENSP00000502814.1 | |||||
| GARS1 | ENST00000675529.1 | n.*1847C>T | 3_prime_UTR_variant | 17/18 | ENSP00000501655.1 | |||||
| GARS1 | ENST00000675859.1 | n.*156C>T | 3_prime_UTR_variant | 14/15 | ENSP00000502033.1 | |||||
| GARS1 | ENST00000676088.1 | n.*1919C>T | 3_prime_UTR_variant | 18/19 | ENSP00000501884.1 | |||||
| GARS1 | ENST00000676140.1 | n.*922C>T | 3_prime_UTR_variant | 16/17 | ENSP00000502571.1 | |||||
| GARS1 | ENST00000676164.1 | n.*1428C>T | 3_prime_UTR_variant | 16/17 | ENSP00000501986.1 | |||||
| GARS1 | ENST00000676210.1 | n.*1266C>T | 3_prime_UTR_variant | 17/18 | ENSP00000502373.1 | |||||
| GARS1 | ENST00000676259.1 | n.*1409C>T | 3_prime_UTR_variant | 16/17 | ENSP00000501980.1 | |||||
| GARS1 | ENST00000676403.1 | n.*62C>T | 3_prime_UTR_variant | 15/16 | ENSP00000502681.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249536Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135378
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727244
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GnomAD4 genome
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
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 | Labcorp Genetics (formerly Invitae), Labcorp | May 01, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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