NM_017866.6(TMEM70):c.211-6_220del AND Mitochondrial complex V (ATP synthase) deficiency nuclear type 2

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 21, 2022
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:: RCV003077637.2

Allele description [Variation Report for NM_017866.6(TMEM70):c.211-6_220del]

NM_017866.6(TMEM70):c.211-6_220del

Gene:

TMEM70:transmembrane protein 70 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

8q21.11

Genomic location:

Preferred name:

NM_017866.6(TMEM70):c.211-6_220del

HGVS:

NC_000008.11:g.73978750_73978765del
NG_016618.1:g.7609_7624del
NM_001040613.3:c.211-6_220del
NM_017866.6:c.211-6_220delMANE SELECT
NC_000008.10:g.74890974_74890989del
NC_000008.10:g.74890985_74891000del

Molecular consequence:

NM_001040613.3:c.211-6_220del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_017866.6:c.211-6_220del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Mitochondrial complex V (ATP synthase) deficiency nuclear type 2
Synonyms:: ENCEPHALOCARDIOMYOPATHY, MITOCHONDRIAL, NEONATAL, DUE TO ATP SYNTHASE DEFICIENCY; MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, TMEM70 TYPE; Nuclearly-encoded mitochondrial complex V (ATP synthase) deficiency 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013546; MedGen: C3279699; Orphanet: 1194; OMIM: 614052

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003462849	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 21, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 18953340, 21147908, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003462849

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 21, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.

Cízková A, Stránecký V, Mayr JA, Tesarová M, Havlícková V, Paul J, Ivánek R, Kuss AW, Hansíková H, Kaplanová V, Vrbacký M, Hartmannová H, Nosková L, Honzík T, Drahota Z, Magner M, Hejzlarová K, Sperl W, Zeman J, Houstek J, Kmoch S.

Nat Genet. 2008 Nov;40(11):1288-90. doi: 10.1038/ng.246. Epub 2008 Oct 26.

PubMed [citation]

PMID:: 18953340

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003462849.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with TMEM70-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant results in the deletion of part of exon 2 (c.211-6_220del) of the TMEM70 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TMEM70 are known to be pathogenic (PMID: 18953340, 21147908).

#	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: Feb 20, 2024

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