Variant chr22-46335587-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000441818.5(TRMU):c.-178G>A 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 0.00806 in 694,158 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 193 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 40 hom. )

Consequence

TRMU
ENST00000441818.5 5_prime_UTR, NMD_transcript

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.82

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 -16 ACMG points.

BP6

Variant 22-46335587-G-A is Benign according to our data. Variant chr22-46335587-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 341994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
TRMU	ENST00000441818.5 linkuse as main transcript	c.-178G>A	5_prime_UTR_variant, NMD_transcript_variant	1/10	1
TRMU	ENST00000456595.5 linkuse as main transcript	c.-178G>A	5_prime_UTR_variant, NMD_transcript_variant	1/9	1
TRMU	ENST00000381021.7 linkuse as main transcript	c.-178G>A	5_prime_UTR_variant, NMD_transcript_variant	1/10	2

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4149

AN:

151944

Hom.:

194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0942

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0168

GnomAD4 exome

AF:

0.00265

AC:

1437

AN:

542096

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

657

AN XY:

283702

show subpopulations

Gnomad4 AFR exome

AF:

0.0818

Gnomad4 AMR exome

AF:

0.00620

Gnomad4 ASJ exome

AF:

0.00501

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000332

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000319

Gnomad4 OTH exome

AF:

0.00688

GnomAD4 genome

AF:

0.0273

AC:

4157

AN:

152062

Hom.:

193

Cov.:

AF XY:

0.0263

AC XY:

1956

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0941

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0311

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.82

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: -3

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