Genetic Variant TRMU:c.-36C>A (chr22-46335729-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018006.5(TRMU):c.-36C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRMU
NM_018006.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
mitochondrial myopathy with reversible cytochrome C oxidase deficiency
Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

TRMU links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018006.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRMU	NM_018006.5	MANE Select	c.-36C>A	5_prime_UTR	Exon 1 of 11	NP_060476.2
TRMU	NM_001282785.2		c.-36C>A	5_prime_UTR	Exon 1 of 10	NP_001269714.1	O75648-2
TRMU	NM_001282782.2		c.-271C>A	5_prime_UTR	Exon 1 of 10	NP_001269711.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRMU	ENST00000645190.1	MANE Select	c.-36C>A	5_prime_UTR	Exon 1 of 11	ENSP00000496496.1	O75648-1
TRMU	ENST00000441818.5	TSL:1	n.-36C>A	non_coding_transcript_exon	Exon 1 of 10	ENSP00000393014.1	Q2PPL5
TRMU	ENST00000456595.5	TSL:1	n.-36C>A	non_coding_transcript_exon	Exon 1 of 9	ENSP00000413880.1	Q2PPL5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1387830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685108

African (AFR)

AF:

0.00

AC:

AN:

31316

American (AMR)

AF:

0.00

AC:

AN:

35862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25108

East Asian (EAS)

AF:

0.00

AC:

AN:

35676

South Asian (SAS)

AF:

0.00

AC:

AN:

79208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5100

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078020

Other (OTH)

AF:

0.00

AC:

AN:

57784

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

1.2

PromoterAI

0.11

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over