NM_018292.5:c.32C>T

Variant names:

• chr6-106640356-C-T
• rs36016898
• NM_018292.5:c.32C>T

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). 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
• Publications: 16 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018292.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QRSL1	NM_018292.5	MANE Select	c.32C>T	p.Ala11Val	missense	Exon 2 of 11	NP_060762.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QRSL1	ENST00000369046.8	TSL:1 MANE Select	c.32C>T	p.Ala11Val	missense	Exon 2 of 11	ENSP00000358042.4	Q9H0R6-1
	QRSL1	ENST00000893160.1		c.32C>T	p.Ala11Val	missense	Exon 2 of 12	ENSP00000563219.1
	QRSL1	ENST00000971598.1		c.32C>T	p.Ala11Val	missense	Exon 2 of 11	ENSP00000641657.1

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

GnomAD2 exomes AF: 0.0680 AC: 17045 AN: 250710 AF XY: 0.0639

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 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

African (AFR) AF: 0.189 AC: 6279 AN: 33242

American (AMR) AF: 0.0765 AC: 3410 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 1970 AN: 26090

East Asian (EAS) AF: 0.0549 AC: 2176 AN: 39622

South Asian (SAS) AF: 0.0263 AC: 2271 AN: 86190

European-Finnish (FIN) AF: 0.0619 AC: 3301 AN: 53368

Middle Eastern (MID) AF: 0.112 AC: 646 AN: 5758

European-Non Finnish (NFE) AF: 0.0592 AC: 65712 AN: 1109440

Other (OTH) AF: 0.0685 AC: 4131 AN: 60284

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

African (AFR) AF: 0.188 AC: 7730 AN: 41112

American (AMR) AF: 0.0832 AC: 1255 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3468

East Asian (EAS) AF: 0.0585 AC: 300 AN: 5132

South Asian (SAS) AF: 0.0255 AC: 122 AN: 4792

European-Finnish (FIN) AF: 0.0736 AC: 761 AN: 10338

Middle Eastern (MID) AF: 0.0799 AC: 23 AN: 288

European-Non Finnish (NFE) AF: 0.0614 AC: 4171 AN: 67934

Other (OTH) AF: 0.0914 AC: 192 AN: 2100

Alfa AF: 0.0727 Hom.: 1732

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.65
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.036
Sift	Benign	0.27	T
Sift4G	Benign	0.26	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
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36016898; hg19: chr6-107088231; COSMIC: COSV107455931; COSMIC: COSV107455931;