rs758434035

Variant names:

• chr7-30595083-C-A
• NM_002047.4:c.162C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-30595083-C-A
• chr7-30595083-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002047.4(GARS1):​c.162C>A​(p.Ser54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GARS1 NM_002047.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1027703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4	c.162C>A	p.Ser54Arg	missense_variant	Exon 1 of 17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.-1C>A		5_prime_UTR_variant	Exon 1 of 17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.162C>A	p.Ser54Arg	missense_variant	Exon 1 of 17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.162C>A	p.Ser54Arg	missense_variant	Exon 1 of 17			ENSP00000502513.1
GARS1	ENST00000675810.1	c.162C>A	p.Ser54Arg	missense_variant	Exon 1 of 16			ENSP00000502743.1
GARS1	ENST00000675693.1	c.19-25C>A		intron_variant	Intron 1 of 17			ENSP00000502174.1
GARS1	ENST00000675051.1	c.22-3713C>A		intron_variant	Intron 1 of 16			ENSP00000502296.1
GARS1	ENST00000674815.1	c.-148+131C>A		intron_variant	Intron 1 of 16			ENSP00000502799.1
GARS1	ENST00000674851.1	c.-183-25C>A		intron_variant	Intron 1 of 17			ENSP00000502451.1
GARS1	ENST00000444666.6	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502681.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394368 Hom.: 0 Cov.: 36 AF XY: 0.00000145 AC XY: 1 AN XY: 689206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.23e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.82	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.68	N;.
REVEL	Benign	0.14
Sift	Benign	0.23	T;.
Sift4G	Benign	0.50	T;D
Polyphen		0.13	B;.
Vest4		0.17
MutPred		0.18		Loss of phosphorylation at S54 (P = 0.0085);Loss of phosphorylation at S54 (P = 0.0085);
MVP		0.23
MPC		0.39
ClinPred		0.35	T
GERP RS		2.8
Varity_R		0.27
gMVP		0.45

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-30634699;