GeneBe

rs2072236

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002047.4(GARS1):​c.222+5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

GARS1
NM_002047.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00004720
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GARS1NM_002047.4 linkuse as main transcriptc.222+5C>A splice_region_variant, intron_variant ENST00000389266.8 NP_002038.2 P41250-1
GARS1NM_001316772.1 linkuse as main transcriptc.60+5C>A splice_region_variant, intron_variant NP_001303701.1 P41250-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GARS1ENST00000389266.8 linkuse as main transcriptc.222+5C>A splice_region_variant, intron_variant 1 NM_002047.4 ENSP00000373918.3 P41250-1
GARS1ENST00000675651.1 linkuse as main transcriptc.222+5C>A splice_region_variant, intron_variant ENSP00000502513.1 A0A6Q8PGZ8
GARS1ENST00000675810.1 linkuse as main transcriptc.222+5C>A splice_region_variant, intron_variant ENSP00000502743.1 A0A6Q8PHH9
GARS1ENST00000675693.1 linkuse as main transcriptc.54+5C>A splice_region_variant, intron_variant ENSP00000502174.1 A0A6Q8PGA8
GARS1ENST00000675051.1 linkuse as main transcriptc.22-3648C>A intron_variant ENSP00000502296.1 A0A6Q8PGI6
GARS1ENST00000674815.1 linkuse as main transcriptc.-148+196C>A intron_variant ENSP00000502799.1 A0A6Q8PGW4
GARS1ENST00000674851.1 linkuse as main transcriptc.-148+5C>A splice_region_variant, intron_variant ENSP00000502451.1 A0A6Q8PGW4
GARS1ENST00000444666.6 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant 3 ENSP00000415447.2 H7C443
GARS1ENST00000674616.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000502408.1 A0A6Q8PGT3
GARS1ENST00000674643.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000501636.1 A0A6Q8PF45
GARS1ENST00000674737.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000502464.1 A0A6Q8PGZ9
GARS1ENST00000674807.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000502814.1 A0A6Q8PFZ6
GARS1ENST00000675529.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000501655.1 A0A6Q8PFN0
GARS1ENST00000675859.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000502033.1 A0A6Q8PFZ6
GARS1ENST00000676088.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000501884.1 A0A6Q8PFN0
GARS1ENST00000676140.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000502571.1 A0A6Q8PH49
GARS1ENST00000676164.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000501986.1 A0A6Q8PFV5
GARS1ENST00000676210.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000502373.1 A0A6Q8PGN7
GARS1ENST00000676259.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000501980.1 A0A6Q8PFU7
GARS1ENST00000676403.1 linkuse as main transcriptn.222+5C>A splice_region_variant, intron_variant ENSP00000502681.1 A0A6Q8PHI7

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
35
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
13
DANN
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000047
dbscSNV1_RF
Benign
0.0080
SpliceAI score (max)
0.33
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.33
Position offset: 1

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: rs2072236; hg19: chr7-30634764; API