6-106641544-A-T

Position:

• chr6-106641544-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018292.5(QRSL1):​c.283+623A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 152,242 control chromosomes in the GnomAD database, including 735 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 0.084 (735 hom., cov: 33)
• Consequence: QRSL1 NM_018292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRSL1	NM_018292.5	c.283+623A>T		intron_variant		ENST00000369046.8	NP_060762.3
QRSL1	XM_011535924.3	c.10+623A>T		intron_variant			XP_011534226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QRSL1	ENST00000369046.8	c.283+623A>T		intron_variant		1	NM_018292.5	ENSP00000358042.4
QRSL1	ENST00000369044.1	c.283+623A>T		intron_variant		2		ENSP00000358040.1

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12769 AN: 152124 Hom.: 734 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0840 AC: 12781 AN: 152242 Hom.: 735 Cov.: 33 AF XY: 0.0867 AC XY: 6452 AN XY: 74446

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0588 Hom.: 34

Bravo AF: 0.0887

Asia WGS AF: 0.164 AC: 570 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.79

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: rs12660628; hg19: chr6-107089419;