chr19-10702688-T-C

Variant names:

• chr19-10702688-T-C
• rs4425006
• NM_031209.3:c.451+434T>C

Variant summary

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

The NM_031209.3(QTRT1):​c.451+434T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 149,928 control chromosomes in the GnomAD database, including 66,439 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 0.94 (66439 hom., cov: 25)
• Consequence: QTRT1 NM_031209.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 10 publications found

Genes affected

QTRT1 (HGNC:23797): (queuine tRNA-ribosyltransferase catalytic subunit 1) This gene encodes the catalytic 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. A pseudogene of this gene is located on the long arm of chromosome X. [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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031209.3. 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
	QTRT1	NM_031209.3	MANE Select	c.451+434T>C		intron	N/A	NP_112486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QTRT1	ENST00000250237.10	TSL:1 MANE Select	c.451+434T>C		intron	N/A	ENSP00000250237.4
	QTRT1	ENST00000592254.1	TSL:3	c.394+434T>C		intron	N/A	ENSP00000468811.1
	QTRT1	ENST00000421333.6	TSL:2	n.451+434T>C		intron	N/A	ENSP00000389126.2

Frequencies

GnomAD3 genomes AF: 0.941 AC: 140941 AN: 149810 Hom.: 66380 Cov.: 25

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.934

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

GnomAD4 genome AF: 0.941 AC: 141060 AN: 149928 Hom.: 66439 Cov.: 25 AF XY: 0.940 AC XY: 68558 AN XY: 72922

African (AFR) AF: 0.980 AC: 39942 AN: 40748

American (AMR) AF: 0.933 AC: 13845 AN: 14846

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3265 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5119 AN: 5120

South Asian (SAS) AF: 0.979 AC: 4692 AN: 4794

European-Finnish (FIN) AF: 0.917 AC: 8955 AN: 9770

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62234 AN: 67894

Other (OTH) AF: 0.934 AC: 1951 AN: 2088

Alfa AF: 0.928 Hom.: 82827

Bravo AF: 0.942

Asia WGS AF: 0.986 AC: 3427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.75
DANN	Benign	0.80
PhyloP100		-0.23
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: rs4425006; hg19: chr19-10813364;