rs752464405

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002047.4(GARS1):​c.1737C>T​(p.Phe579Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,840 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: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

GARS1
NM_002047.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.421
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
Variant 7-30628597-C-T is Benign according to our data. Variant chr7-30628597-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.421 with no splicing effect.
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GARS1NM_002047.4 linkuse as main transcriptc.1737C>T p.Phe579Phe synonymous_variant 14/17 ENST00000389266.8 NP_002038.2 P41250-1
GARS1NM_001316772.1 linkuse as main transcriptc.1575C>T p.Phe525Phe synonymous_variant 14/17 NP_001303701.1 P41250-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GARS1ENST00000389266.8 linkuse as main transcriptc.1737C>T p.Phe579Phe synonymous_variant 14/171 NM_002047.4 ENSP00000373918.3 P41250-1
GARS1ENST00000675651.1 linkuse as main transcriptc.1737C>T p.Phe579Phe synonymous_variant 14/17 ENSP00000502513.1 A0A6Q8PGZ8
GARS1ENST00000675810.1 linkuse as main transcriptc.1635C>T p.Phe545Phe synonymous_variant 13/16 ENSP00000502743.1 A0A6Q8PHH9
GARS1ENST00000675693.1 linkuse as main transcriptc.1569C>T p.Phe523Phe synonymous_variant 15/18 ENSP00000502174.1 A0A6Q8PGA8
GARS1ENST00000675051.1 linkuse as main transcriptc.1536C>T p.Phe512Phe synonymous_variant 14/17 ENSP00000502296.1 A0A6Q8PGI6
GARS1ENST00000674815.1 linkuse as main transcriptc.1368C>T p.Phe456Phe synonymous_variant 14/17 ENSP00000502799.1 A0A6Q8PGW4
GARS1ENST00000674851.1 linkuse as main transcriptc.1368C>T p.Phe456Phe synonymous_variant 15/18 ENSP00000502451.1 A0A6Q8PGW4
GARS1ENST00000444666.6 linkuse as main transcriptn.*158C>T non_coding_transcript_exon_variant 15/183 ENSP00000415447.2 H7C443
GARS1ENST00000674616.1 linkuse as main transcriptn.*1451C>T non_coding_transcript_exon_variant 15/18 ENSP00000502408.1 A0A6Q8PGT3
GARS1ENST00000674643.1 linkuse as main transcriptn.*837C>T non_coding_transcript_exon_variant 15/17 ENSP00000501636.1 A0A6Q8PF45
GARS1ENST00000674737.1 linkuse as main transcriptn.*1075C>T non_coding_transcript_exon_variant 15/18 ENSP00000502464.1 A0A6Q8PGZ9
GARS1ENST00000674807.1 linkuse as main transcriptn.*10C>T non_coding_transcript_exon_variant 13/16 ENSP00000502814.1 A0A6Q8PFZ6
GARS1ENST00000675529.1 linkuse as main transcriptn.*1607C>T non_coding_transcript_exon_variant 15/18 ENSP00000501655.1 A0A6Q8PFN0
GARS1ENST00000675859.1 linkuse as main transcriptn.*10C>T non_coding_transcript_exon_variant 13/15 ENSP00000502033.1 A0A6Q8PFZ6
GARS1ENST00000676088.1 linkuse as main transcriptn.*1679C>T non_coding_transcript_exon_variant 16/19 ENSP00000501884.1 A0A6Q8PFN0
GARS1ENST00000676140.1 linkuse as main transcriptn.*682C>T non_coding_transcript_exon_variant 14/17 ENSP00000502571.1 A0A6Q8PH49
GARS1ENST00000676164.1 linkuse as main transcriptn.*1188C>T non_coding_transcript_exon_variant 14/17 ENSP00000501986.1 A0A6Q8PFV5
GARS1ENST00000676210.1 linkuse as main transcriptn.*1026C>T non_coding_transcript_exon_variant 15/18 ENSP00000502373.1 A0A6Q8PGN7
GARS1ENST00000676259.1 linkuse as main transcriptn.*1169C>T non_coding_transcript_exon_variant 14/17 ENSP00000501980.1 A0A6Q8PFU7
GARS1ENST00000676403.1 linkuse as main transcriptn.1737C>T non_coding_transcript_exon_variant 14/16 ENSP00000502681.1 A0A6Q8PHI7
GARS1ENST00000444666.6 linkuse as main transcriptn.*158C>T 3_prime_UTR_variant 15/183 ENSP00000415447.2 H7C443
GARS1ENST00000674616.1 linkuse as main transcriptn.*1451C>T 3_prime_UTR_variant 15/18 ENSP00000502408.1 A0A6Q8PGT3
GARS1ENST00000674643.1 linkuse as main transcriptn.*837C>T 3_prime_UTR_variant 15/17 ENSP00000501636.1 A0A6Q8PF45
GARS1ENST00000674737.1 linkuse as main transcriptn.*1075C>T 3_prime_UTR_variant 15/18 ENSP00000502464.1 A0A6Q8PGZ9
GARS1ENST00000674807.1 linkuse as main transcriptn.*10C>T 3_prime_UTR_variant 13/16 ENSP00000502814.1 A0A6Q8PFZ6
GARS1ENST00000675529.1 linkuse as main transcriptn.*1607C>T 3_prime_UTR_variant 15/18 ENSP00000501655.1 A0A6Q8PFN0
GARS1ENST00000675859.1 linkuse as main transcriptn.*10C>T 3_prime_UTR_variant 13/15 ENSP00000502033.1 A0A6Q8PFZ6
GARS1ENST00000676088.1 linkuse as main transcriptn.*1679C>T 3_prime_UTR_variant 16/19 ENSP00000501884.1 A0A6Q8PFN0
GARS1ENST00000676140.1 linkuse as main transcriptn.*682C>T 3_prime_UTR_variant 14/17 ENSP00000502571.1 A0A6Q8PH49
GARS1ENST00000676164.1 linkuse as main transcriptn.*1188C>T 3_prime_UTR_variant 14/17 ENSP00000501986.1 A0A6Q8PFV5
GARS1ENST00000676210.1 linkuse as main transcriptn.*1026C>T 3_prime_UTR_variant 15/18 ENSP00000502373.1 A0A6Q8PGN7
GARS1ENST00000676259.1 linkuse as main transcriptn.*1169C>T 3_prime_UTR_variant 14/17 ENSP00000501980.1 A0A6Q8PFU7

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249578
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135406
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1460646
Hom.:
0
Cov.:
30
AF XY:
0.00000963
AC XY:
7
AN XY:
726614
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000151
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 11, 2019This 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. -
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitterclinical testingMolecular Genetics Laboratory, London Health Sciences Centre-- -
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 21, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.25
CADD
Benign
11
DANN
Benign
0.59
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs752464405; hg19: chr7-30668213; API