rs1777000992

Variant names:

• chr6-106640501-T-C
• rs1777000992
• NM_018292.5:c.177T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_018292.5(QRSL1):​c.177T>C​(p.Tyr59Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: QRSL1 NM_018292.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.283
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-106640501-T-C is Benign according to our data. Variant chr6-106640501-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2872656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.283 with no splicing effect.

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.177T>C	p.Tyr59Tyr	synonymous	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.177T>C	p.Tyr59Tyr	synonymous	Exon 2 of 11	ENSP00000358042.4	Q9H0R6-1
	QRSL1	ENST00000893160.1		c.177T>C	p.Tyr59Tyr	synonymous	Exon 2 of 12	ENSP00000563219.1
	QRSL1	ENST00000971598.1		c.177T>C	p.Tyr59Tyr	synonymous	Exon 2 of 11	ENSP00000641657.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.75
PhyloP100		-0.28

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: rs1777000992; hg19: chr6-107088376;