NM_002047.4:c.174G>C

Variant names:

• chr7-30595095-G-C
• rs747227947
• NM_002047.4:c.174G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002047.4(GARS1):​c.174G>C​(p.Ala58Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,890 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. Synonymous variant affecting the same amino acid position (i.e. A58A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GARS1 NM_002047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-0.534 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002047.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	NM_002047.4	MANE Select	c.174G>C	p.Ala58Ala	synonymous	Exon 1 of 17	NP_002038.2
	GARS1	NM_001316772.1		c.12G>C	p.Ala4Ala	synonymous	Exon 1 of 17	NP_001303701.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	ENST00000389266.8	TSL:1 MANE Select	c.174G>C	p.Ala58Ala	synonymous	Exon 1 of 17	ENSP00000373918.3
	GARS1	ENST00000675651.1		c.174G>C	p.Ala58Ala	synonymous	Exon 1 of 17	ENSP00000502513.1
	GARS1	ENST00000675810.1		c.174G>C	p.Ala58Ala	synonymous	Exon 1 of 16	ENSP00000502743.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390890 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 687152

African (AFR) AF: 0.00 AC: 0 AN: 32026

American (AMR) AF: 0.00 AC: 0 AN: 36548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25212

East Asian (EAS) AF: 0.00 AC: 0 AN: 36306

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081866

Other (OTH) AF: 0.00 AC: 0 AN: 58102

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		-0.53
PromoterAI		0.067	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747227947; hg19: chr7-30634711;