rs367915362

Variant names:

• chr7-30601102-G-A
• rs367915362
• NM_002047.4:c.471G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-30601102-G-A
• chr7-30601102-G-C

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.471G>A​(p.Leu157Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GARS1 NM_002047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73
• Publications: 1 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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 2D

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• neuronopathy, distal hereditary motor, type 5A

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, Laboratory for Molecular Medicine
• spinal muscular atrophy, infantile, James type

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

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 (BayesDel_noAF=-0.37).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4	c.471G>A	p.Leu157Leu	synonymous_variant	Exon 4 of 17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.309G>A	p.Leu103Leu	synonymous_variant	Exon 4 of 17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.471G>A	p.Leu157Leu	synonymous_variant	Exon 4 of 17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.471G>A	p.Leu157Leu	synonymous_variant	Exon 4 of 17			ENSP00000502513.1
GARS1	ENST00000675810.1	c.369G>A	p.Leu123Leu	synonymous_variant	Exon 3 of 16			ENSP00000502743.1
GARS1	ENST00000675693.1	c.303G>A	p.Leu101Leu	synonymous_variant	Exon 5 of 18			ENSP00000502174.1
GARS1	ENST00000675051.1	c.270G>A	p.Leu90Leu	synonymous_variant	Exon 4 of 17			ENSP00000502296.1
GARS1	ENST00000674815.1	c.102G>A	p.Leu34Leu	synonymous_variant	Exon 4 of 17			ENSP00000502799.1
GARS1	ENST00000674851.1	c.102G>A	p.Leu34Leu	synonymous_variant	Exon 5 of 18			ENSP00000502451.1
GARS1	ENST00000444666.6	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*185G>A		non_coding_transcript_exon_variant	Exon 5 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*341G>A		non_coding_transcript_exon_variant	Exon 5 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.*341G>A		non_coding_transcript_exon_variant	Exon 5 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 18			ENSP00000502373.1
GARS1	ENST00000676403.1	n.471G>A		non_coding_transcript_exon_variant	Exon 4 of 16			ENSP00000502681.1
GARS1	ENST00000674616.1	n.*185G>A		3_prime_UTR_variant	Exon 5 of 18			ENSP00000502408.1
GARS1	ENST00000675529.1	n.*341G>A		3_prime_UTR_variant	Exon 5 of 18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.*341G>A		3_prime_UTR_variant	Exon 5 of 19			ENSP00000501884.1
GARS1	ENST00000676259.1	n.428-27G>A		intron_variant	Intron 3 of 16			ENSP00000501980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.7
DANN	Benign	0.79
PhyloP100		5.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs367915362; hg19: chr7-30640718; COSMIC: COSV101220050;