Variant chr6-106640893-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_018292.5(QRSL1):c.255G>A(p.Glu85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000739 in 1,613,558 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00037 ( 3 hom. )

Consequence

QRSL1
NM_018292.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.11

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 6-106640893-G-A is Benign according to our data. Variant chr6-106640893-G-A is described in ClinVar as [Benign]. Clinvar id is 720366.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.11 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00426 (648/152250) while in subpopulation AFR AF= 0.0149 (617/41542). AF 95% confidence interval is 0.0139. There are 1 homozygotes in gnomad4. There are 309 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QRSL1	NM_018292.5 linkuse as main transcript	c.255G>A	p.Glu85=	synonymous_variant	3/11	ENST00000369046.8
QRSL1	XM_011535924.3 linkuse as main transcript	c.-19G>A		5_prime_UTR_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QRSL1	ENST00000369046.8 linkuse as main transcript	c.255G>A	p.Glu85=	synonymous_variant	3/11	1	NM_018292.5	P1	Q9H0R6-1
QRSL1	ENST00000369044.1 linkuse as main transcript	c.255G>A	p.Glu85=	synonymous_variant	3/7	2
QRSL1	ENST00000467262.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

648

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00104

AC:

262

AN:

251256

Hom.:

AF XY:

0.000817

AC XY:

111

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000372

AC:

544

AN:

1461308

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

235

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000630

GnomAD4 genome

AF:

0.00426

AC:

648

AN:

152250

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00476

Asia WGS

AF:

0.000867

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

QRSL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.3

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over