rs758434035

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002047.4(GARS1):​c.162C>T​(p.Ser54Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,394,368 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: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

GARS1
NM_002047.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.937
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 -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 7-30595083-C-T is Benign according to our data. Variant chr7-30595083-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 574424.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.937 with no splicing effect.
BS2
High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GARS1NM_002047.4 linkuse as main transcriptc.162C>T p.Ser54Ser synonymous_variant 1/17 ENST00000389266.8 NP_002038.2 P41250-1
GARS1NM_001316772.1 linkuse as main transcriptc.-1C>T 5_prime_UTR_variant 1/17 NP_001303701.1 P41250-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GARS1ENST00000389266.8 linkuse as main transcriptc.162C>T p.Ser54Ser synonymous_variant 1/171 NM_002047.4 ENSP00000373918.3 P41250-1
GARS1ENST00000675651.1 linkuse as main transcriptc.162C>T p.Ser54Ser synonymous_variant 1/17 ENSP00000502513.1 A0A6Q8PGZ8
GARS1ENST00000675810.1 linkuse as main transcriptc.162C>T p.Ser54Ser synonymous_variant 1/16 ENSP00000502743.1 A0A6Q8PHH9
GARS1ENST00000675693.1 linkuse as main transcriptc.19-25C>T intron_variant ENSP00000502174.1 A0A6Q8PGA8
GARS1ENST00000675051.1 linkuse as main transcriptc.22-3713C>T intron_variant ENSP00000502296.1 A0A6Q8PGI6
GARS1ENST00000674815.1 linkuse as main transcriptc.-148+131C>T intron_variant ENSP00000502799.1 A0A6Q8PGW4
GARS1ENST00000674851.1 linkuse as main transcriptc.-183-25C>T intron_variant ENSP00000502451.1 A0A6Q8PGW4
GARS1ENST00000444666.6 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/183 ENSP00000415447.2 H7C443
GARS1ENST00000674616.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/18 ENSP00000502408.1 A0A6Q8PGT3
GARS1ENST00000674643.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/17 ENSP00000501636.1 A0A6Q8PF45
GARS1ENST00000674737.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/18 ENSP00000502464.1 A0A6Q8PGZ9
GARS1ENST00000674807.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/16 ENSP00000502814.1 A0A6Q8PFZ6
GARS1ENST00000675529.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/18 ENSP00000501655.1 A0A6Q8PFN0
GARS1ENST00000675859.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/15 ENSP00000502033.1 A0A6Q8PFZ6
GARS1ENST00000676088.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/19 ENSP00000501884.1 A0A6Q8PFN0
GARS1ENST00000676140.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/17 ENSP00000502571.1 A0A6Q8PH49
GARS1ENST00000676164.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/17 ENSP00000501986.1 A0A6Q8PFV5
GARS1ENST00000676210.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/18 ENSP00000502373.1 A0A6Q8PGN7
GARS1ENST00000676259.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/17 ENSP00000501980.1 A0A6Q8PFU7
GARS1ENST00000676403.1 linkuse as main transcriptn.162C>T non_coding_transcript_exon_variant 1/16 ENSP00000502681.1 A0A6Q8PHI7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000669
AC:
1
AN:
149544
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
81326
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:
0.0000164
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000186
AC:
26
AN:
1394368
Hom.:
0
Cov.:
36
AF XY:
0.0000145
AC XY:
10
AN XY:
689206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000231
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 27, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
16
DANN
Benign
0.97
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs758434035; hg19: chr7-30634699; API