7-30594882-C-G

Variant names:

• chr7-30594882-C-G
• rs775425723
• NM_002047.4:c.-40C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002047.4(GARS1):​c.-40C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000744 in 1,343,494 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: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: GARS1 NM_002047.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.97

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

ACMG classification

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=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4	c.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	ENST00000389266.8	NP_002038.2
GARS1	NM_002047.4	c.-40C>G		5_prime_UTR_variant	Exon 1 of 17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.-202C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17		NP_001303701.1
GARS1	NM_001316772.1	c.-202C>G		5_prime_UTR_variant	Exon 1 of 17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266	c.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651	c.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17			ENSP00000502513.1
GARS1	ENST00000675810	c.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16			ENSP00000502743.1
GARS1	ENST00000675693	c.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18			ENSP00000502174.1
GARS1	ENST00000674815	c.-218C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17			ENSP00000502799.1
GARS1	ENST00000389266	c.-40C>G		5_prime_UTR_variant	Exon 1 of 17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651	c.-40C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000502513.1
GARS1	ENST00000675810	c.-40C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502743.1
GARS1	ENST00000675693	c.-40C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000502174.1
GARS1	ENST00000674815	c.-218C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000502799.1
GARS1	ENST00000675051.1	c.22-3914C>G		intron_variant	Intron 1 of 16			ENSP00000502296.1
GARS1	ENST00000674616.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17			ENSP00000502571.1
GARS1	ENST00000676210.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.-40C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16			ENSP00000502681.1
GARS1	ENST00000674616.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000502571.1
GARS1	ENST00000676210.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.-40C>G		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502681.1
GARS1	ENST00000674616.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000502571.1
GARS1	ENST00000676210.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.-40C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502681.1
GARS1	ENST00000674851.1	c.-254C>G		upstream_gene_variant				ENSP00000502451.1
GARS1	ENST00000444666.6	n.-40C>G		upstream_gene_variant		3		ENSP00000415447.2
GARS1	ENST00000676164.1	n.-40C>G		upstream_gene_variant				ENSP00000501986.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1343494 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 664742

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: 0.00

Gnomad4 OTH exome AF: 0.0000178

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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

Other links and lift over

dbSNP: rs775425723; hg19: chr7-30634498;