NM_002047.4:c.659-43C>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002047.4(GARS1):c.659-43C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,482,540 control chromosomes in the GnomAD database, including 277,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 21416 hom., cov: 32)

Exomes 𝑓: 0.61 ( 255973 hom. )

Consequence

GARS1
NM_002047.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.151

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-30603453-C-A is Benign according to our data. Variant chr7-30603453-C-A is described in ClinVar as [Benign]. Clinvar id is 258537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.659-43C>A		intron_variant	Intron 5 of 16	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 link	c.497-43C>A		intron_variant	Intron 5 of 16		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 link	c.659-43C>A	intron_variant	Intron 5 of 16	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 link	c.659-43C>A	intron_variant	Intron 5 of 16			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 link	c.557-43C>A	intron_variant	Intron 4 of 15			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 link	c.491-43C>A	intron_variant	Intron 6 of 17			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 link	c.458-43C>A	intron_variant	Intron 5 of 16			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 link	c.290-43C>A	intron_variant	Intron 5 of 16			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 link	c.290-43C>A	intron_variant	Intron 6 of 17			ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 link	n.659-43C>A	intron_variant	Intron 5 of 17	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 link	n.*373-43C>A	intron_variant	Intron 6 of 17			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.659-43C>A	intron_variant	Intron 5 of 16			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.659-43C>A	intron_variant	Intron 5 of 17			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.659-43C>A	intron_variant	Intron 5 of 15			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.*529-43C>A	intron_variant	Intron 6 of 17			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.659-43C>A	intron_variant	Intron 5 of 14			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.*529-43C>A	intron_variant	Intron 6 of 18			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.659-43C>A	intron_variant	Intron 5 of 16			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 link	n.*110-43C>A	intron_variant	Intron 5 of 16			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.659-43C>A	intron_variant	Intron 5 of 17			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.*91-43C>A	intron_variant	Intron 5 of 16			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.659-43C>A	intron_variant	Intron 5 of 15			ENSP00000502681.1	A0A6Q8PHI7

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73395

AN:

151924

Hom.:

21419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.606

Gnomad AMR

AF:

0.534

Gnomad ASJ

AF:

0.683

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.647

Gnomad OTH

AF:

0.514

GnomAD3 exomes

AF:

0.559

AC:

138079

AN:

246982

Hom.:

41015

AF XY:

0.561

AC XY:

75252

AN XY:

134036

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.557

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.488

Gnomad SAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.643

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.611

AC:

812985

AN:

1330496

Hom.:

255973

Cov.:

AF XY:

0.606

AC XY:

405808

AN XY:

669240

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.552

Gnomad4 ASJ exome

AF:

0.669

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.422

Gnomad4 FIN exome

AF:

0.638

Gnomad4 NFE exome

AF:

0.650

Gnomad4 OTH exome

AF:

0.579

GnomAD4 genome

AF:

0.483

AC:

73392

AN:

152044

Hom.:

21416

Cov.:

AF XY:

0.481

AC XY:

35713

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.534

Gnomad4 ASJ

AF:

0.683

Gnomad4 EAS

AF:

0.476

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.644

Gnomad4 NFE

AF:

0.647

Gnomad4 OTH

AF:

0.512

Alfa

AF:

0.525

Hom.:

3357

Bravo

AF:

0.460

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spinal muscular atrophy, infantile, James type

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease type 2D

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neuronopathy, distal hereditary motor, type 5A

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.1

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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