NM_018006.5(TRMU):c.652-2A>G AND Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 10, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003332050.1

Allele description [Variation Report for NM_018006.5(TRMU):c.652-2A>G]

NM_018006.5(TRMU):c.652-2A>G

Gene:

TRMU:tRNA mitochondrial 2-thiouridylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.31

Genomic location:

Preferred name:

NM_018006.5(TRMU):c.652-2A>G

HGVS:

NC_000022.11:g.46352119A>G
NG_012173.1:g.21719A>G
NM_001282782.2:c.310-2A>G
NM_001282783.2:c.232-2A>G
NM_001282784.2:c.232-2A>G
NM_001282785.2:c.652-2A>G
NM_018006.5:c.652-2A>GMANE SELECT
NC_000022.10:g.46748016A>G
NM_018006.4:c.652-2A>G

Molecular consequence:

NM_001282782.2:c.310-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282783.2:c.232-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282784.2:c.232-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282785.2:c.652-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_018006.5:c.652-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins
Synonyms:: Liver failure acute infantile; LIVER FAILURE, INFANTILE, TRANSIENT
Identifiers:: MONDO: MONDO:0013111; MedGen: C3278664; Orphanet: 217371; OMIM: 613070

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Mus musculus BRF1, RNA polymerase III transcription initiation factor 90 kDa sub...
Mus musculus BRF1, RNA polymerase III transcription initiation factor 90 kDa subunit (Brf1), mRNA
gi|118130445|ref|NM_028193.3|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004039003	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Aug 10, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004039003

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Aug 10, 2023)

germline

clinical testing

Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004039003.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: TRMU c.652-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251414 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.652-2A>G in individuals affected with Liver Failure Acute Infantile, Transient and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 30, 2023

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