22-46335127-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000486620.5(TRMU):n.287-2652C>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,090 control chromosomes in the GnomAD database, including 535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.071 (535 hom., cov: 32)
• Consequence: TRMU ENST00000486620.5 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.262

Genes affected

TRMU (HGNC:25481): (tRNA mitochondrial 2-thiouridylase) This nuclear gene encodes a mitochondrial tRNA-modifying enzyme. The encoded protein catalyzes the 2-thiolation of uridine on the wobble positions of tRNA(Lys), tRNA(Glu), and tRNA(Gln), resulting in the formation of 5-taurinomethyl-2-thiouridine moieties. Mutations in this gene may cause transient infantile liver failure. Polymorphisms in this gene may also influence the severity of deafness caused by mitochondrial 12S ribosomal RNA mutations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 22-46335127-C-G is Benign according to our data. Variant chr22-46335127-C-G is described in ClinVar as [Benign]. Clinvar id is 1238890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMU	ENST00000486620.5	n.287-2652C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10781 AN: 151972 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0708 AC: 10774 AN: 152090 Hom.: 535 Cov.: 32 AF XY: 0.0692 AC XY: 5141 AN XY: 74334

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0614

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0411

Gnomad4 FIN AF: 0.0984

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0874 Hom.: 86

Bravo AF: 0.0656

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.3
Dann	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9615953; hg19: chr22-46731024;