chr7-30615951-C-T

Position:

• chr7-30615951-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002047.4(GARS1):​c.1087C>T​(p.Pro363Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: GARS1 NM_002047.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.85

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40695825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4	c.1087C>T	p.Pro363Ser	missense_variant	9/17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.925C>T	p.Pro309Ser	missense_variant	9/17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.1087C>T	p.Pro363Ser	missense_variant	9/17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.1087C>T	p.Pro363Ser	missense_variant	9/17			ENSP00000502513.1
GARS1	ENST00000675810.1	c.985C>T	p.Pro329Ser	missense_variant	8/16			ENSP00000502743.1
GARS1	ENST00000675693.1	c.919C>T	p.Pro307Ser	missense_variant	10/18			ENSP00000502174.1
GARS1	ENST00000675051.1	c.886C>T	p.Pro296Ser	missense_variant	9/17			ENSP00000502296.1
GARS1	ENST00000674815.1	c.718C>T	p.Pro240Ser	missense_variant	9/17			ENSP00000502799.1
GARS1	ENST00000674851.1	c.718C>T	p.Pro240Ser	missense_variant	10/18			ENSP00000502451.1
GARS1	ENST00000444666.6	n.1087C>T		non_coding_transcript_exon_variant	9/18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*801C>T		non_coding_transcript_exon_variant	10/18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*187C>T		non_coding_transcript_exon_variant	10/17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*425C>T		non_coding_transcript_exon_variant	10/18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.1087C>T		non_coding_transcript_exon_variant	9/16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*957C>T		non_coding_transcript_exon_variant	10/18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.1087C>T		non_coding_transcript_exon_variant	9/15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.*1029C>T		non_coding_transcript_exon_variant	11/19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*32C>T		non_coding_transcript_exon_variant	9/17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*538C>T		non_coding_transcript_exon_variant	9/17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*376C>T		non_coding_transcript_exon_variant	10/18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*519C>T		non_coding_transcript_exon_variant	9/17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.1087C>T		non_coding_transcript_exon_variant	9/16			ENSP00000502681.1
GARS1	ENST00000674616.1	n.*801C>T		3_prime_UTR_variant	10/18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*187C>T		3_prime_UTR_variant	10/17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*425C>T		3_prime_UTR_variant	10/18			ENSP00000502464.1
GARS1	ENST00000675529.1	n.*957C>T		3_prime_UTR_variant	10/18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.*1029C>T		3_prime_UTR_variant	11/19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*32C>T		3_prime_UTR_variant	9/17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*538C>T		3_prime_UTR_variant	9/17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*376C>T		3_prime_UTR_variant	10/18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*519C>T		3_prime_UTR_variant	9/17			ENSP00000501980.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74436

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.30	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.44
Sift	Benign	0.069	T
Sift4G	Benign	0.12	T
Polyphen		0.098	B
Vest4		0.22
MutPred		0.68		Loss of methylation at K360 (P = 0.0759);
MVP		0.66
MPC		0.53
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs267601479; hg19: chr7-30655567;