rs14270

Positions:

• chr7-30631471-T-A
• chr7-30631471-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002047.4(GARS1):​c.1833T>A​(p.Val611Val) 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. V611V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GARS1 NM_002047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.932 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4	c.1833T>A	p.Val611Val	synonymous_variant	15/17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.1671T>A	p.Val557Val	synonymous_variant	15/17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.1833T>A	p.Val611Val	synonymous_variant	15/17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.1833T>A	p.Val611Val	synonymous_variant	15/17			ENSP00000502513.1
GARS1	ENST00000675810.1	c.1731T>A	p.Val577Val	synonymous_variant	14/16			ENSP00000502743.1
GARS1	ENST00000675693.1	c.1665T>A	p.Val555Val	synonymous_variant	16/18			ENSP00000502174.1
GARS1	ENST00000675051.1	c.1632T>A	p.Val544Val	synonymous_variant	15/17			ENSP00000502296.1
GARS1	ENST00000674815.1	c.1464T>A	p.Val488Val	synonymous_variant	15/17			ENSP00000502799.1
GARS1	ENST00000674851.1	c.1464T>A	p.Val488Val	synonymous_variant	16/18			ENSP00000502451.1
GARS1	ENST00000444666.6	n.*254T>A		non_coding_transcript_exon_variant	16/18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*1547T>A		non_coding_transcript_exon_variant	16/18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*933T>A		non_coding_transcript_exon_variant	16/17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*1171T>A		non_coding_transcript_exon_variant	16/18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.*106T>A		non_coding_transcript_exon_variant	14/16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*1703T>A		non_coding_transcript_exon_variant	16/18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.*1775T>A		non_coding_transcript_exon_variant	17/19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*778T>A		non_coding_transcript_exon_variant	15/17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*1284T>A		non_coding_transcript_exon_variant	15/17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*1122T>A		non_coding_transcript_exon_variant	16/18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*1265T>A		non_coding_transcript_exon_variant	15/17			ENSP00000501980.1
GARS1	ENST00000444666.6	n.*254T>A		3_prime_UTR_variant	16/18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*1547T>A		3_prime_UTR_variant	16/18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*933T>A		3_prime_UTR_variant	16/17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*1171T>A		3_prime_UTR_variant	16/18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.*106T>A		3_prime_UTR_variant	14/16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*1703T>A		3_prime_UTR_variant	16/18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.*1775T>A		3_prime_UTR_variant	17/19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*778T>A		3_prime_UTR_variant	15/17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*1284T>A		3_prime_UTR_variant	15/17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*1122T>A		3_prime_UTR_variant	16/18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*1265T>A		3_prime_UTR_variant	15/17			ENSP00000501980.1
GARS1	ENST00000675859.1	n.*83-776T>A		intron_variant				ENSP00000502033.1
GARS1	ENST00000676403.1	n.1810-776T>A		intron_variant				ENSP00000502681.1

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	-0.79
CADD	Benign	3.3
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs14270; hg19: chr7-30671087;