rs2529438

Positions:

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_002047.4(GARS1):c.93G>A(p.Leu31Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,580,308 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L31L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GARS1
NM_002047.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.670

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]

GARS1 links:

GARS1 (HGNC:):

GARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-30595014-G-A is Benign according to our data. Variant chr7-30595014-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 390140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.67 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4 linkuse as main transcript	c.93G>A	p.Leu31Leu	synonymous_variant	1/17	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 linkuse as main transcript	c.-70G>A		5_prime_UTR_variant	1/17		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 linkuse as main transcript	c.93G>A	p.Leu31Leu	synonymous_variant	1/17	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 linkuse as main transcript	c.93G>A	p.Leu31Leu	synonymous_variant	1/17			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 linkuse as main transcript	c.93G>A	p.Leu31Leu	synonymous_variant	1/16			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 linkuse as main transcript	c.18+75G>A		intron_variant				ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 linkuse as main transcript	c.22-3782G>A		intron_variant				ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 linkuse as main transcript	c.-148+62G>A		intron_variant				ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 linkuse as main transcript	c.-184+62G>A		intron_variant				ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/18	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/16			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/15			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/17			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/17			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/16			ENSP00000502681.1	A0A6Q8PHI7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428188

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709234

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:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.4

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over