7-30595081-A-G

Variant names:

• chr7-30595081-A-G
• rs1414091099
• NM_002047.4:c.160A>G
• GARS1 p.Ser54Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002047.4(GARS1):​c.160A>G​(p.Ser54Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. S54S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GARS1 NM_002047.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.112386584).

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.160A>G	p.Ser54Gly	missense	Exon 1 of 17	NP_002038.2	P41250-1
	GARS1	NM_001316772.1		c.-3A>G		5_prime_UTR	Exon 1 of 17	NP_001303701.1	P41250-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	ENST00000389266.8	TSL:1 MANE Select	c.160A>G	p.Ser54Gly	missense	Exon 1 of 17	ENSP00000373918.3	P41250-1
	GARS1	ENST00000675651.1		c.160A>G	p.Ser54Gly	missense	Exon 1 of 17	ENSP00000502513.1	A0A6Q8PGZ8
	GARS1	ENST00000675810.1		c.160A>G	p.Ser54Gly	missense	Exon 1 of 16	ENSP00000502743.1	A0A6Q8PHH9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000665 AC: 1 AN: 150340 AF XY: 0.0000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000162

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395104 Hom.: 0 Cov.: 36 AF XY: 0.00000145 AC XY: 1 AN XY: 689640

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32234

American (AMR) AF: 0.00 AC: 0 AN: 37146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25232

East Asian (EAS) AF: 0.00 AC: 0 AN: 36626

South Asian (SAS) AF: 0.00 AC: 0 AN: 80218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1084106

Other (OTH) AF: 0.00 AC: 0 AN: 58302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.72	T
PhyloP100		2.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.21
Sift	Benign	0.20	T
Sift4G	Benign	0.38	T
PromoterAI		-0.014	Neutral
Varity_R		0.26
gMVP		0.29
Mutation Taster		=83/17	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1414091099;

hg19: chr7-30634697;