3-49098923-C-G

Variant names:

• chr3-49098923-C-G
• NM_005051.3:c.1825G>C

Variant summary

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

The NM_005051.3(QARS1):​c.1825G>C​(p.Ala609Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: QARS1 NM_005051.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881

Genes affected

QARS1 (HGNC:9751): (glutaminyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. In metazoans, 9 aminoacyl-tRNA synthetases specific for glutamine (gln), glutamic acid (glu), and 7 other amino acids are associated within a multienzyme complex. Although present in eukaryotes, glutaminyl-tRNA synthetase (QARS) is absent from many prokaryotes, mitochondria, and chloroplasts, in which Gln-tRNA(Gln) is formed by transamidation of the misacylated Glu-tRNA(Gln). Glutaminyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

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=0.264542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QARS1	NM_005051.3	c.1825G>C	p.Ala609Pro	missense_variant	Exon 19 of 24	ENST00000306125.12	NP_005042.1
QARS1	NM_001272073.2	c.1792G>C	p.Ala598Pro	missense_variant	Exon 19 of 24		NP_001259002.1
QARS1	XM_017006965.3	c.1825G>C	p.Ala609Pro	missense_variant	Exon 19 of 23		XP_016862454.2
QARS1	NR_073590.2	n.1800G>C		non_coding_transcript_exon_variant	Exon 19 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QARS1	ENST00000306125.12	c.1825G>C	p.Ala609Pro	missense_variant	Exon 19 of 24	1	NM_005051.3	ENSP00000307567.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461848 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727234

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: 0.00000180

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
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;T;.;T;T
Eigen	Benign	0.0034
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.4	N;N;N;.;.
REVEL	Benign	0.13
Sift	Uncertain	0.010	D;D;D;.;.
Sift4G	Uncertain	0.024	D;T;T;D;T
Polyphen		0.16	.;B;.;.;.
Vest4		0.46, 0.50, 0.43
MutPred		0.63		.;Loss of stability (P = 0.129);.;.;.;
MVP		0.57
MPC		0.52
ClinPred		0.51	D
GERP RS		3.8
Varity_R		0.42
gMVP		0.65

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: chr3-49136356;