ENST00000675810:c.-45C>G

Variant names:

• chr7-30594877-C-G
• rs903029869
• ENST00000675810:c.-45C>G

Variant summary

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

The ENST00000675810(GARS1):​c.-45C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GARS1 ENST00000675810 5_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.351

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=-0.42).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_001316772.1	c.-207C>G		5_prime_UTR_variant	Exon 1 of 17		NP_001303701.1
GARS1	NM_002047.4	c.-45C>G		upstream_gene_variant		ENST00000389266.8	NP_002038.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000675810	c.-45C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502743.1
GARS1	ENST00000674815	c.-223C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000502799.1
GARS1	ENST00000675051.1	c.22-3919C>G		intron_variant	Intron 1 of 16			ENSP00000502296.1
GARS1	ENST00000674643.1	n.-45C>G		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501636.1
GARS1	ENST00000674807.1	n.-45C>G		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.-45C>G		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.-45C>G		non_coding_transcript_exon_variant	Exon 1 of 19			ENSP00000501884.1
GARS1	ENST00000676210.1	n.-45C>G		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502373.1
GARS1	ENST00000676403.1	n.-45C>G		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502681.1
GARS1	ENST00000674643.1	n.-45C>G		5_prime_UTR_variant	Exon 1 of 17			ENSP00000501636.1
GARS1	ENST00000674807.1	n.-45C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.-45C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.-45C>G		5_prime_UTR_variant	Exon 1 of 19			ENSP00000501884.1
GARS1	ENST00000676210.1	n.-45C>G		5_prime_UTR_variant	Exon 1 of 18			ENSP00000502373.1
GARS1	ENST00000676403.1	n.-45C>G		5_prime_UTR_variant	Exon 1 of 16			ENSP00000502681.1
GARS1	ENST00000389266.8	c.-45C>G		upstream_gene_variant		1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.-45C>G		upstream_gene_variant				ENSP00000502513.1
GARS1	ENST00000675693.1	c.-45C>G		upstream_gene_variant				ENSP00000502174.1
GARS1	ENST00000674851.1	c.-259C>G		upstream_gene_variant				ENSP00000502451.1
GARS1	ENST00000444666.6	n.-45C>G		upstream_gene_variant		3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.-45C>G		upstream_gene_variant				ENSP00000502408.1
GARS1	ENST00000674737.1	n.-45C>G		upstream_gene_variant				ENSP00000502464.1
GARS1	ENST00000675859.1	n.-45C>G		upstream_gene_variant				ENSP00000502033.1
GARS1	ENST00000676140.1	n.-45C>G		upstream_gene_variant				ENSP00000502571.1
GARS1	ENST00000676164.1	n.-45C>G		upstream_gene_variant				ENSP00000501986.1
GARS1	ENST00000676259.1	n.-45C>G		upstream_gene_variant				ENSP00000501980.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Charcot-Marie-Tooth disease type 2D;CN031873:Neuronopathy, distal hereditary motor, type 5A Other:1

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GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.86

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: rs903029869; hg19: chr7-30634493;