6-106640710-T-A

Position:

• chr6-106640710-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018292.5(QRSL1):​c.185-113T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,082,212 control chromosomes in the GnomAD database, including 158,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (21579 hom., cov: 32)
  • Exomes 𝑓: 0.54 (137213 hom.)
• Consequence: QRSL1 NM_018292.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.55

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 6-106640710-T-A is Benign according to our data. Variant chr6-106640710-T-A is described in ClinVar as [Benign]. Clinvar id is 1273153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QRSL1	NM_018292.5	c.185-113T>A		intron_variant		ENST00000369046.8
QRSL1	XM_011535924.3	c.-89-113T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QRSL1	ENST00000369046.8	c.185-113T>A		intron_variant		1	NM_018292.5	P1
QRSL1	ENST00000369044.1	c.185-113T>A		intron_variant		2
QRSL1	ENST00000467262.1	n.374-113T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80028 AN: 151938 Hom.: 21550 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.536 AC: 498644 AN: 930156 Hom.: 137213 AF XY: 0.531 AC XY: 251846 AN XY: 474446

Gnomad4 AFR exome AF: 0.529

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.568

Gnomad4 NFE exome AF: 0.570

Gnomad4 OTH exome AF: 0.520

GnomAD4 genome AF: 0.527 AC: 80102 AN: 152056 Hom.: 21579 Cov.: 32 AF XY: 0.520 AC XY: 38643 AN XY: 74324

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.507

Alfa AF: 0.564 Hom.: 3026

Bravo AF: 0.522

Asia WGS AF: 0.366 AC: 1271 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.82

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: rs2306098; hg19: chr6-107088585; COSMIC: COSV64687141; COSMIC: COSV64687141;