NM_018292.5:c.255G>A

Variant names:

• chr6-106640893-G-A
• rs56974135
• NM_018292.5:c.255G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_018292.5(QRSL1):​c.255G>A​(p.Glu85Glu) 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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.11
• Publications: 0 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.255G>A	p.Glu85Glu	synonymous	Exon 3 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.255G>A	p.Glu85Glu	synonymous	Exon 3 of 11	ENSP00000358042.4	Q9H0R6-1
	QRSL1	ENST00000893160.1		c.255G>A	p.Glu85Glu	synonymous	Exon 3 of 12	ENSP00000563219.1
	QRSL1	ENST00000971598.1		c.255G>A	p.Glu85Glu	synonymous	Exon 3 of 11	ENSP00000641657.1

Frequencies

GnomAD3 genomes AF: 0.00426 AC: 648 AN: 152132 Hom.: 1 Cov.: 33

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

GnomAD2 exomes AF: 0.00104 AC: 262 AN: 251256 AF XY: 0.000817

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 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.: 3 Cov.: 30 AF XY: 0.000323 AC XY: 235 AN XY: 726986

African (AFR) AF: 0.0135 AC: 453 AN: 33462

American (AMR) AF: 0.000984 AC: 44 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111670

Other (OTH) AF: 0.000630 AC: 38 AN: 60364

GnomAD4 genome AF: 0.00426 AC: 648 AN: 152250 Hom.: 1 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74438

African (AFR) AF: 0.0149 AC: 617 AN: 41542

American (AMR) AF: 0.00150 AC: 23 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00161 Hom.: 1

Bravo AF: 0.00476

Asia WGS AF: 0.000867 AC: 3 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	QRSL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.3
DANN	Benign	0.58
PhyloP100		3.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs56974135; hg19: chr6-107088768;