Genetic Variant GARS1:c.22-4071G>A (chr7-30594725-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000675051.1(GARS1):c.22-4071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000669 in 597,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

GARS1
ENST00000675051.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.769

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-DT (HGNC:48951): (GARS1 divergent transcript)

GARS1-DT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.-197G>A		upstream_gene_variant		ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 link	c.-359G>A		upstream_gene_variant			NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARS1	ENST00000675051.1 link	c.22-4071G>A	intron_variant	Intron 1 of 16			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000389266.8 link	c.-197G>A	upstream_gene_variant		1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 link	c.-197G>A	upstream_gene_variant				ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 link	c.-197G>A	upstream_gene_variant				ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 link	c.-197G>A	upstream_gene_variant				ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000674815.1 link	c.-375G>A	upstream_gene_variant				ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 link	c.-411G>A	upstream_gene_variant				ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 link	n.-197G>A	upstream_gene_variant		3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 link	n.-197G>A	upstream_gene_variant				ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.-197G>A	upstream_gene_variant				ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.-197G>A	upstream_gene_variant				ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.-197G>A	upstream_gene_variant				ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.-197G>A	upstream_gene_variant				ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.-197G>A	upstream_gene_variant				ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.-197G>A	upstream_gene_variant				ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.-197G>A	upstream_gene_variant				ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 link	n.-197G>A	upstream_gene_variant				ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.-197G>A	upstream_gene_variant				ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.-197G>A	upstream_gene_variant				ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.-197G>A	upstream_gene_variant				ENSP00000502681.1	A0A6Q8PHI7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

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:

0.00000673

AC:

AN:

445546

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

235456

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:

0.0000111

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.93

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over