Variant chr22-46335678-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000441818.5(TRMU):c.-87T>C variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,454,302 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 44 hom. )

Consequence

TRMU
ENST00000441818.5 5_prime_UTR, NMD_transcript

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -2.80

Variant links:

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]

TRMU links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 22-46335678-T-C is Benign according to our data. Variant chr22-46335678-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 342001.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00209 (316/151314) while in subpopulation EAS AF= 0.0197 (100/5074). AF 95% confidence interval is 0.0166. There are 7 homozygotes in gnomad4. There are 214 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMU	NM_018006.5 linkuse as main transcript			upstream_gene_variant		ENST00000645190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMU	ENST00000645190.1 linkuse as main transcript			upstream_gene_variant			NM_018006.5	P1	O75648-1

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

314

AN:

151200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.0197

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.00190

AC:

2471

AN:

1302988

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1235

AN XY:

646358

show subpopulations

Gnomad4 AFR exome

AF:

0.000105

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.0410

Gnomad4 SAS exome

AF:

0.000182

Gnomad4 FIN exome

AF:

0.0133

Gnomad4 NFE exome

AF:

0.000426

Gnomad4 OTH exome

AF:

0.00168

GnomAD4 genome

AF:

0.00209

AC:

316

AN:

151314

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

214

AN XY:

74022

show subpopulations

Gnomad4 AFR

AF:

0.0000729

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.0197

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.0122

Gnomad4 NFE

AF:

0.00102

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.000612

Asia WGS

AF:

0.0190

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.17

DANN

Benign

0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over