6-106640356-C-T

Position:

• chr6-106640356-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018292.5(QRSL1):​c.32C>T​(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 1,609,742 control chromosomes in the GnomAD database, including 4,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.099 (1012 hom., cov: 31)
  • Exomes 𝑓: 0.062 (3260 hom.)
• Consequence: QRSL1 NM_018292.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.649

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017118156).
• BP6: Variant 6-106640356-C-T is Benign according to our data. Variant chr6-106640356-C-T is described in ClinVar as [Benign]. Clinvar id is 1264753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRSL1	NM_018292.5	c.32C>T	p.Ala11Val	missense_variant	2/11	ENST00000369046.8	NP_060762.3
QRSL1	XM_011535924.3	c.-242C>T		5_prime_UTR_variant	3/12		XP_011534226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QRSL1	ENST00000369046.8	c.32C>T	p.Ala11Val	missense_variant	2/11	1	NM_018292.5	ENSP00000358042.4
QRSL1	ENST00000369044.1	c.32C>T	p.Ala11Val	missense_variant	2/7	2		ENSP00000358040.1
QRSL1	ENST00000467262.1	n.221C>T		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14887 AN: 151050 Hom.: 1010 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0801

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0919

GnomAD3 exomes AF: 0.0680 AC: 17045 AN: 250710 Hom.: 792 AF XY: 0.0639 AC XY: 8663 AN XY: 135618

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.0758

Gnomad ASJ exome AF: 0.0785

Gnomad EAS exome AF: 0.0537

Gnomad SAS exome AF: 0.0262

Gnomad FIN exome AF: 0.0636

Gnomad NFE exome AF: 0.0624

Gnomad OTH exome AF: 0.0672

GnomAD4 exome AF: 0.0616 AC: 89896 AN: 1458576 Hom.: 3260 Cov.: 32 AF XY: 0.0601 AC XY: 43597 AN XY: 725804

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0765

Gnomad4 ASJ exome AF: 0.0755

Gnomad4 EAS exome AF: 0.0549

Gnomad4 SAS exome AF: 0.0263

Gnomad4 FIN exome AF: 0.0619

Gnomad4 NFE exome AF: 0.0592

Gnomad4 OTH exome AF: 0.0685

GnomAD4 genome AF: 0.0986 AC: 14905 AN: 151166 Hom.: 1012 Cov.: 31 AF XY: 0.0979 AC XY: 7213 AN XY: 73700

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0832

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.0585

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0705 Hom.: 730

Bravo AF: 0.105

TwinsUK AF: 0.0634 AC: 235

ALSPAC AF: 0.0506 AC: 195

ESP6500AA AF: 0.179 AC: 789

ESP6500EA AF: 0.0626 AC: 538

ExAC AF: 0.0697 AC: 8465

Asia WGS AF: 0.0510 AC: 178 AN: 3478

EpiCase AF: 0.0642

EpiControl AF: 0.0693

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.77	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.036
Sift	Benign	0.27	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0	B;.
Vest4		0.084
MPC		0.19
ClinPred		0.018	T
GERP RS		3.9
Varity_R		0.10
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs36016898; hg19: chr6-107088231;