7-30594959-GC-CT

Position:

• chr7-30594959-GC-CT

Variant summary

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

The NM_002047.4(GARS1):​c.38_39delGCinsCT​(p.Arg13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GARS1 NM_002047.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4	c.38_39delGCinsCT	p.Arg13Pro	missense_variant		ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.-125_-124delGCinsCT		5_prime_UTR_variant	1/17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.38_39delGCinsCT	p.Arg13Pro	missense_variant		1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.38_39delGCinsCT	p.Arg13Pro	missense_variant				ENSP00000502513.1
GARS1	ENST00000675810.1	c.38_39delGCinsCT	p.Arg13Pro	missense_variant				ENSP00000502743.1
GARS1	ENST00000675693.1	c.18+20_18+21delGCinsCT		intron_variant				ENSP00000502174.1
GARS1	ENST00000675051.1	c.22-3837_22-3836delGCinsCT		intron_variant				ENSP00000502296.1
GARS1	ENST00000674815.1	c.-148+7_-148+8delGCinsCT		splice_region_variant, intron_variant				ENSP00000502799.1
GARS1	ENST00000674851.1	c.-184+7_-184+8delGCinsCT		splice_region_variant, intron_variant				ENSP00000502451.1
GARS1	ENST00000444666.6	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.38_39delGCinsCT		non_coding_transcript_exon_variant	1/16			ENSP00000502681.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 2 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 04, 2023

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 13 of the GARS protein (p.Arg13Pro). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with GARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 476757). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554336495; hg19: chr7-30634575;