NM_024996.7(GFM1):c.424del (p.Val142fs) AND Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 26, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000272222.7

Allele description [Variation Report for NM_024996.7(GFM1):c.424del (p.Val142fs)]

NM_024996.7(GFM1):c.424del (p.Val142fs)

Gene:

GFM1:G elongation factor mitochondrial 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3q25.32

Genomic location:

Preferred name:

NM_024996.7(GFM1):c.424del (p.Val142fs)

HGVS:

NC_000003.12:g.158646799del
NG_008441.1:g.7272del
NM_001308164.2:c.424del
NM_001308166.2:c.424del
NM_001374355.1:c.424del
NM_001374356.1:c.424del
NM_001374357.1:c.199del
NM_001374358.1:c.234+1018del
NM_001374359.1:c.5+1018del
NM_001374360.1:c.5+1018del
NM_001374361.1:c.5+1018del
NM_024996.7:c.424delMANE SELECT
NP_001295093.1:p.Val142fs
NP_001295095.1:p.Val142fs
NP_001361284.1:p.Val142fs
NP_001361285.1:p.Val142fs
NP_001361286.1:p.Val67fs
NP_079272.4:p.Val142fs
NC_000003.11:g.158364588del
NM_024996.5:c.424delG
NM_024996.7:c.424del
NR_164499.1:n.532del
NR_164500.1:n.532del
NR_164502.1:n.532del

Protein change:

V142fs

Links:

dbSNP: rs886058120

NCBI 1000 Genomes Browser:

rs886058120

Molecular consequence:

NM_001308164.2:c.424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001308166.2:c.424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374355.1:c.424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374356.1:c.424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374357.1:c.199del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024996.7:c.424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374358.1:c.234+1018del - intron variant - [Sequence Ontology: SO:0001627]
NM_001374359.1:c.5+1018del - intron variant - [Sequence Ontology: SO:0001627]
NM_001374360.1:c.5+1018del - intron variant - [Sequence Ontology: SO:0001627]
NM_001374361.1:c.5+1018del - intron variant - [Sequence Ontology: SO:0001627]
NR_164499.1:n.532del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164500.1:n.532del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164502.1:n.532del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1
Synonyms:: HEPATOENCEPHALOPATHY, EARLY FATAL PROGRESSIVE; Combined oxidative phosphorylation deficiency 1
Identifiers:: MONDO: MONDO:0012191; MedGen: C1836797; OMIM: 609060

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000441852	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV004199299	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 26, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000441852

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV004199299

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 26, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000441852.3

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

Description

The GFM1 c.424delG (p.Val142SerfsTer15) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for combined oxidative phosphorylation deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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

From Baylor Genetics, SCV004199299.1

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

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

Last Updated: Sep 29, 2024

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