chr7-30632320-C-G

Variant names:

• chr7-30632320-C-G
• rs746028145
• NM_002047.4:c.1977C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002047.4(GARS1):​c.1977C>G​(p.Ala659Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. A659A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GARS1 NM_002047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• 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 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4	c.1977C>G	p.Ala659Ala	synonymous_variant	Exon 16 of 17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.1815C>G	p.Ala605Ala	synonymous_variant	Exon 16 of 17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.1977C>G	p.Ala659Ala	synonymous_variant	Exon 16 of 17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.1995C>G	p.Ala665Ala	synonymous_variant	Exon 16 of 17			ENSP00000502513.1
GARS1	ENST00000675810.1	c.1875C>G	p.Ala625Ala	synonymous_variant	Exon 15 of 16			ENSP00000502743.1
GARS1	ENST00000675693.1	c.1809C>G	p.Ala603Ala	synonymous_variant	Exon 17 of 18			ENSP00000502174.1
GARS1	ENST00000675051.1	c.1776C>G	p.Ala592Ala	synonymous_variant	Exon 16 of 17			ENSP00000502296.1
GARS1	ENST00000674815.1	c.1608C>G	p.Ala536Ala	synonymous_variant	Exon 16 of 17			ENSP00000502799.1
GARS1	ENST00000674851.1	c.1608C>G	p.Ala536Ala	synonymous_variant	Exon 17 of 18			ENSP00000502451.1
GARS1	ENST00000444666.6	n.*398C>G		non_coding_transcript_exon_variant	Exon 17 of 18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*1691C>G		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*1782C>G		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*1315C>G		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.*250C>G		non_coding_transcript_exon_variant	Exon 15 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*1847C>G		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.*156C>G		non_coding_transcript_exon_variant	Exon 14 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.*1919C>G		non_coding_transcript_exon_variant	Exon 18 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*922C>G		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*1428C>G		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*1266C>G		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*1409C>G		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.*62C>G		non_coding_transcript_exon_variant	Exon 15 of 16			ENSP00000502681.1
GARS1	ENST00000444666.6	n.*398C>G		3_prime_UTR_variant	Exon 17 of 18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*1691C>G		3_prime_UTR_variant	Exon 17 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*1782C>G		3_prime_UTR_variant	Exon 16 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*1315C>G		3_prime_UTR_variant	Exon 17 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.*250C>G		3_prime_UTR_variant	Exon 15 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*1847C>G		3_prime_UTR_variant	Exon 17 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.*156C>G		3_prime_UTR_variant	Exon 14 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.*1919C>G		3_prime_UTR_variant	Exon 18 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*922C>G		3_prime_UTR_variant	Exon 16 of 17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*1428C>G		3_prime_UTR_variant	Exon 16 of 17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*1266C>G		3_prime_UTR_variant	Exon 17 of 18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*1409C>G		3_prime_UTR_variant	Exon 16 of 17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.*62C>G		3_prime_UTR_variant	Exon 15 of 16			ENSP00000502681.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

Other links and lift over

dbSNP: rs746028145; hg19: chr7-30671936;