7-30594837-C-T

Variant names:

• chr7-30594837-C-T
• rs777045330
• ENST00000675810.1:c.-85C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001316772.1(GARS1):​c.-247C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000946 in 1,057,328 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: 33)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: GARS1 NM_001316772.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• 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-DT (HGNC:48951): (GARS1 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316772.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	NM_001316772.1		c.-247C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	NP_001303701.1	P41250-2
	GARS1	NM_001316772.1		c.-247C>T		5_prime_UTR	Exon 1 of 17	NP_001303701.1	P41250-2
	GARS1	NM_002047.4	MANE Select	c.-85C>T		upstream_gene	N/A	NP_002038.2	P41250-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	ENST00000675810.1		c.-85C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000502743.1	A0A6Q8PHH9
	GARS1	ENST00000675810.1		c.-85C>T		5_prime_UTR	Exon 1 of 16	ENSP00000502743.1	A0A6Q8PHH9
	GARS1	ENST00000675051.1		c.22-3959C>T		intron	N/A	ENSP00000502296.1	A0A6Q8PGI6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.46e-7 AC: 1 AN: 1057328 Hom.: 0 Cov.: 14 AF XY: 0.00000188 AC XY: 1 AN XY: 530864

African (AFR) AF: 0.00 AC: 0 AN: 23756

American (AMR) AF: 0.00 AC: 0 AN: 27968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21570

East Asian (EAS) AF: 0.00 AC: 0 AN: 33232

South Asian (SAS) AF: 0.00 AC: 0 AN: 68856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3410

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 799204

Other (OTH) AF: 0.00 AC: 0 AN: 46344

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	0.98
PhyloP100		1.9
PromoterAI		-0.25	Neutral

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: rs777045330; hg19: chr7-30634453;