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. Synonymous variant affecting the same amino acid position (i.e. A11A) has been classified as Likely benign.

• 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]

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	UniProt
QRSL1	NM_018292.5	c.32C>T	p.Ala11Val	missense_variant	2/11	ENST00000369046.8
QRSL1	XM_011535924.3	c.-242C>T		5_prime_UTR_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QRSL1	ENST00000369046.8	c.32C>T	p.Ala11Val	missense_variant	2/11	1	NM_018292.5	P1
QRSL1	ENST00000369044.1	c.32C>T	p.Ala11Val	missense_variant	2/7	2
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;.
MutationTaster	Benign	0.022	P;P
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;