rs3127657

Variant names:

• chr6-106656499-T-C
• rs3127657
• NM_018292.5:c.1160+767T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-106656499-T-C
• chr6-106656499-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018292.5(QRSL1):​c.1160+767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,010 control chromosomes in the GnomAD database, including 24,076 homozygotes. 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 0.56 (24076 hom., cov: 33)
• Consequence: QRSL1 NM_018292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 7 publications found

Genes affected

QRSL1 (HGNC:21020): (glutaminyl-tRNA amidotransferase subunit QRSL1) Enables glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity. Involved in glutaminyl-tRNAGln biosynthesis via transamidation and mitochondrial translation. Located in mitochondrion. Part of glutamyl-tRNA(Gln) amidotransferase complex. Implicated in combined oxidative phosphorylation deficiency 40. [provided by Alliance of Genome Resources, Apr 2022]

QRSL1 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 40

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QRSL1	NM_018292.5	c.1160+767T>C		intron_variant	Intron 9 of 10	ENST00000369046.8	NP_060762.3
QRSL1	XM_011535924.3	c.887+767T>C		intron_variant	Intron 10 of 11		XP_011534226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QRSL1	ENST00000369046.8	c.1160+767T>C		intron_variant	Intron 9 of 10	1	NM_018292.5	ENSP00000358042.4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84904 AN: 151892 Hom.: 24042 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.539

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 84983 AN: 152010 Hom.: 24076 Cov.: 33 AF XY: 0.557 AC XY: 41410 AN XY: 74292

African (AFR) AF: 0.538 AC: 22302 AN: 41428

American (AMR) AF: 0.574 AC: 8774 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1573 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2147 AN: 5176

South Asian (SAS) AF: 0.407 AC: 1963 AN: 4820

European-Finnish (FIN) AF: 0.649 AC: 6859 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39698 AN: 67956

Other (OTH) AF: 0.544 AC: 1149 AN: 2114

Alfa AF: 0.564 Hom.: 10185

Bravo AF: 0.557

Asia WGS AF: 0.465 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		-0.027
Mutation Taster		=100/0	polymorphism (auto)

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: rs3127657; hg19: chr6-107104374;