rs150213018

Variant names:

• chr7-30594966-TCTG-T
• rs150213018
• NM_002047.4:c.59_61delTGC

Your query was ambiguous. Multiple possible variants found:

• chr7-30594966-TCTG-T
• chr7-30594966-TCTG-TCTGCTG
• chr7-30594966-TCTG-TCTGCTGCTG

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_002047.4(GARS1):​c.59_61delTGC​(p.Leu20del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,432,794 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GARS1 NM_002047.4 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:4
• 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: Likely_benign. The variant received -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_002047.4
• BP6: Variant 7-30594966-TCTG-T is Benign according to our data. Variant chr7-30594966-TCTG-T is described in ClinVar as Benign. ClinVar VariationId is 416092.Status of the report is criteria_provided_single_submitter, 1 stars.

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.59_61delTGC	p.Leu20del	disruptive_inframe_deletion	Exon 1 of 17	NP_002038.2	P41250-1
	GARS1	NM_001316772.1		c.-104_-102delTGC		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.59_61delTGC	p.Leu20del	disruptive_inframe_deletion	Exon 1 of 17	ENSP00000373918.3	P41250-1
	GARS1	ENST00000675651.1		c.59_61delTGC	p.Leu20del	disruptive_inframe_deletion	Exon 1 of 17	ENSP00000502513.1	A0A6Q8PGZ8
	GARS1	ENST00000675810.1		c.59_61delTGC	p.Leu20del	disruptive_inframe_deletion	Exon 1 of 16	ENSP00000502743.1	A0A6Q8PHH9

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151984 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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00202 AC: 405 AN: 200818 AF XY: 0.00211

Gnomad AFR exome AF: 0.00456

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00143

Gnomad EAS exome AF: 0.00145

Gnomad FIN exome AF: 0.00233

Gnomad NFE exome AF: 0.00239

Gnomad OTH exome AF: 0.000774

GnomAD4 exome AF: 0.000190 AC: 272 AN: 1432794 Hom.: 0 AF XY: 0.000226 AC XY: 161 AN XY: 713094

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

African (AFR) AF: 0.000121 AC: 4 AN: 33130

American (AMR) AF: 0.000730 AC: 32 AN: 43846

Ashkenazi Jewish (ASJ) AF: 0.000426 AC: 11 AN: 25808

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39252

South Asian (SAS) AF: 0.000484 AC: 41 AN: 84788

European-Finnish (FIN) AF: 0.000688 AC: 27 AN: 39248

Middle Eastern (MID) AF: 0.000393 AC: 2 AN: 5092

European-Non Finnish (NFE) AF: 0.000125 AC: 138 AN: 1102066

Other (OTH) AF: 0.000201 AC: 12 AN: 59564

⚠️ 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 Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151984 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74248

African (AFR) AF: 0.00 AC: 0 AN: 41410

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: 10576

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

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

Alfa AF: 0.00274 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 2 (1)
-	-	1	GARS1-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150213018; hg19: chr7-30634582; COSMIC: COSV66827768; COSMIC: COSV66827768;