rs78980639

Variant names:

• chr7-30594745-T-A
• rs78980639
• ENST00000675051.1:c.22-4051T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-30594745-T-A
• chr7-30594745-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001316772.1(GARS1):​c.-339T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000443 in 451,736 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: 0.0000044 (0 hom.)
• Consequence: GARS1 NM_001316772.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

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.-339T>A		5_prime_UTR	Exon 1 of 17	NP_001303701.1	P41250-2
	GARS1	NM_002047.4	MANE Select	c.-177T>A		upstream_gene	N/A	NP_002038.2	P41250-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GARS1	ENST00000675051.1		c.22-4051T>A		intron	N/A	ENSP00000502296.1	A0A6Q8PGI6
	GARS1-DT	ENST00000578994.6	TSL:4	n.65A>T		non_coding_transcript_exon	Exon 1 of 5
	GARS1-DT	ENST00000579174.5	TSL:3	n.64A>T		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000443 AC: 2 AN: 451736 Hom.: 0 Cov.: 5 AF XY: 0.00000838 AC XY: 2 AN XY: 238612

African (AFR) AF: 0.00 AC: 0 AN: 10888

American (AMR) AF: 0.00 AC: 0 AN: 18724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13384

East Asian (EAS) AF: 0.00 AC: 0 AN: 29396

South Asian (SAS) AF: 0.00 AC: 0 AN: 45684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2016

European-Non Finnish (NFE) AF: 0.00000725 AC: 2 AN: 275970

Other (OTH) AF: 0.00 AC: 0 AN: 26030

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		-0.18
PromoterAI		-0.034	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: rs78980639; hg19: chr7-30634361;