chr3-114065036-T-G

Variant names:

• chr3-114065036-T-G
• rs16861476
• NM_024638.4:c.-21-201T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024638.4(QTRT2):​c.-21-201T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 152,288 control chromosomes in the GnomAD database, including 482 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.076 (482 hom., cov: 32)
• Consequence: QTRT2 NM_024638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 4 publications found

Genes affected

QTRT2 (HGNC:25771): (queuine tRNA-ribosyltransferase accessory subunit 2) This gene encodes a subunit of tRNA-guanine transglycosylase. tRNA-guanine transglycosylase is a heterodimeric enzyme complex that plays a critical role in tRNA modification by synthesizing the 7-deazaguanosine queuosine, which is found in tRNAs that code for asparagine, aspartic acid, histidine, and tyrosine. The encoded protein may play a role in the queuosine 5'-monophosphate salvage pathway. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024638.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QTRT2	NM_024638.4	MANE Select	c.-21-201T>G		intron	N/A	NP_078914.1
	QTRT2	NM_001256835.2		c.16-201T>G		intron	N/A	NP_001243764.1
	QTRT2	NM_001256836.2		c.16-5590T>G		intron	N/A	NP_001243765.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QTRT2	ENST00000281273.8	TSL:1 MANE Select	c.-21-201T>G		intron	N/A	ENSP00000281273.4
	QTRT2	ENST00000485050.5	TSL:1	c.16-201T>G		intron	N/A	ENSP00000420682.1
	QTRT2	ENST00000493014.1	TSL:2	c.16-5590T>G		intron	N/A	ENSP00000419169.1

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11535 AN: 152168 Hom.: 481 Cov.: 32

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0915

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0869

Gnomad OTH AF: 0.0856

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0758 AC: 11538 AN: 152288 Hom.: 482 Cov.: 32 AF XY: 0.0751 AC XY: 5588 AN XY: 74452

African (AFR) AF: 0.0679 AC: 2822 AN: 41552

American (AMR) AF: 0.0620 AC: 948 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0915 AC: 317 AN: 3466

East Asian (EAS) AF: 0.0517 AC: 268 AN: 5186

South Asian (SAS) AF: 0.0509 AC: 246 AN: 4830

European-Finnish (FIN) AF: 0.0655 AC: 695 AN: 10612

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5916 AN: 68026

Other (OTH) AF: 0.0847 AC: 179 AN: 2114

Alfa AF: 0.0832 Hom.: 727

Bravo AF: 0.0764

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		0.42
PromoterAI		0.0057	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs16861476; hg19: chr3-113783883;