7-30594966-TCTG-TCTGCTGCTG

Variant names:

• chr7-30594966-T-TCTGCTG
• rs150213018
• NM_002047.4:c.56_61dupTGCTGC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_002047.4(GARS1):​c.56_61dupTGCTGC​(p.Leu19_Leu20dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000653 in 1,593,314 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: GARS1 NM_002047.4 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 2.30
• Publications: 2 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: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002047.4
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000329 (5/151998) while in subpopulation NFE AF = 0.0000736 (5/67976). AF 95% confidence interval is 0.0000285. There are 0 homozygotes in GnomAd4. There are 0 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5 AD gene.

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.56_61dupTGCTGC	p.Leu19_Leu20dup	disruptive_inframe_insertion	Exon 1 of 17	NP_002038.2	P41250-1
	GARS1	NM_001316772.1		c.-107_-102dupTGCTGC		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.56_61dupTGCTGC	p.Leu19_Leu20dup	disruptive_inframe_insertion	Exon 1 of 17	ENSP00000373918.3	P41250-1
	GARS1	ENST00000675651.1		c.56_61dupTGCTGC	p.Leu19_Leu20dup	disruptive_inframe_insertion	Exon 1 of 17	ENSP00000502513.1	A0A6Q8PGZ8
	GARS1	ENST00000675810.1		c.56_61dupTGCTGC	p.Leu19_Leu20dup	disruptive_inframe_insertion	Exon 1 of 16	ENSP00000502743.1	A0A6Q8PHH9

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151998 Hom.: 0 Cov.: 33

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: 0.0000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000299 AC: 6 AN: 200818 AF XY: 0.0000358

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000316

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000556

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000687 AC: 99 AN: 1441316 Hom.: 0 Cov.: 30 AF XY: 0.0000795 AC XY: 57 AN XY: 717226

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.0000226 AC: 1 AN: 44272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5126

European-Non Finnish (NFE) AF: 0.0000839 AC: 93 AN: 1108468

Other (OTH) AF: 0.0000668 AC: 4 AN: 59896

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151998 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74256

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000642

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	1	-	Charcot-Marie-Tooth disease type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=86/14	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs150213018; hg19: chr7-30634582;