22-46335604-A-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000441818.5(TRMU):c.-161A>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 0.000161 in 805,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
TRMU
ENST00000441818.5 5_prime_UTR, NMD_transcript
ENST00000441818.5 5_prime_UTR, NMD_transcript
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.564
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TRMU | ENST00000441818.5 | c.-161A>C | 5_prime_UTR_variant, NMD_transcript_variant | 1/10 | 1 | ||||
| TRMU | ENST00000456595.5 | c.-161A>C | 5_prime_UTR_variant, NMD_transcript_variant | 1/9 | 1 | ||||
| TRMU | ENST00000381021.7 | c.-161A>C | 5_prime_UTR_variant, NMD_transcript_variant | 1/10 | 2 |
Frequencies
GnomAD3 genomes 0.000132 AC: 20AN: 151808Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000168 AC: 110AN: 653498Hom.: 0 Cov.: 9 AF XY: 0.000204 AC XY: 69AN XY: 338854
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GnomAD4 genome 0.000132 AC: 20AN: 151808Hom.: 0 Cov.: 33 AF XY: 0.0000809 AC XY: 6AN XY: 74144
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
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 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at