chr7-30601081-T-C

Position:

• chr7-30601081-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP7 BS2

The NM_002047.4(GARS1):​c.450T>C​(p.Phe150Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,772 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GARS1 NM_002047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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 Benign. Variant got -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.2 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4	c.450T>C	p.Phe150Phe	synonymous_variant	4/17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.288T>C	p.Phe96Phe	synonymous_variant	4/17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.450T>C	p.Phe150Phe	synonymous_variant	4/17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.450T>C	p.Phe150Phe	synonymous_variant	4/17			ENSP00000502513.1
GARS1	ENST00000675810.1	c.348T>C	p.Phe116Phe	synonymous_variant	3/16			ENSP00000502743.1
GARS1	ENST00000675693.1	c.282T>C	p.Phe94Phe	synonymous_variant	5/18			ENSP00000502174.1
GARS1	ENST00000675051.1	c.249T>C	p.Phe83Phe	synonymous_variant	4/17			ENSP00000502296.1
GARS1	ENST00000674815.1	c.81T>C	p.Phe27Phe	synonymous_variant	4/17			ENSP00000502799.1
GARS1	ENST00000674851.1	c.81T>C	p.Phe27Phe	synonymous_variant	5/18			ENSP00000502451.1
GARS1	ENST00000444666.6	n.450T>C		non_coding_transcript_exon_variant	4/18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*164T>C		non_coding_transcript_exon_variant	5/18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.450T>C		non_coding_transcript_exon_variant	4/17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.450T>C		non_coding_transcript_exon_variant	4/18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.450T>C		non_coding_transcript_exon_variant	4/16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*320T>C		non_coding_transcript_exon_variant	5/18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.450T>C		non_coding_transcript_exon_variant	4/15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.*320T>C		non_coding_transcript_exon_variant	5/19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.450T>C		non_coding_transcript_exon_variant	4/17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.450T>C		non_coding_transcript_exon_variant	4/17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.450T>C		non_coding_transcript_exon_variant	4/18			ENSP00000502373.1
GARS1	ENST00000676403.1	n.450T>C		non_coding_transcript_exon_variant	4/16			ENSP00000502681.1
GARS1	ENST00000674616.1	n.*164T>C		3_prime_UTR_variant	5/18			ENSP00000502408.1
GARS1	ENST00000675529.1	n.*320T>C		3_prime_UTR_variant	5/18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.*320T>C		3_prime_UTR_variant	5/19			ENSP00000501884.1
GARS1	ENST00000676259.1	n.428-48T>C		intron_variant				ENSP00000501980.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000200 AC: 5 AN: 249554 Hom.: 0 AF XY: 0.0000295 AC XY: 4 AN XY: 135398

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461772 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727200

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: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.4
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs751505742; hg19: chr7-30640697;