NM_002490.6(NDUFA6):c.191G>C (p.Arg64Pro) AND Mitochondrial complex 1 deficiency, nuclear type 33

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 13, 2018
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000709997.3

Allele description [Variation Report for NM_002490.6(NDUFA6):c.191G>C (p.Arg64Pro)]

NM_002490.6(NDUFA6):c.191G>C (p.Arg64Pro)

Gene:

NDUFA6:NADH:ubiquinone oxidoreductase subunit A6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.2

Genomic location:

Preferred name:

NM_002490.6(NDUFA6):c.191G>C (p.Arg64Pro)

HGVS:

NC_000022.11:g.42087124C>G
NG_051973.1:g.8832G>C
NM_002490.6:c.191G>CMANE SELECT
NP_002481.3:p.Arg64Pro
NC_000022.10:g.42483128C>G
NM_002490.4:c.269G>C
NM_002490.5:c.191G>C

Protein change:

R64P; ARG64PRO

Links:

OMIM: 602138.0001; dbSNP: rs750830935

NCBI 1000 Genomes Browser:

rs750830935

Molecular consequence:

NM_002490.6:c.191G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mitochondrial complex 1 deficiency, nuclear type 33
Synonyms:: MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 33
Identifiers:: MONDO: MONDO:0032636; MedGen: C4748840; OMIM: 618253

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000840362	OMIM	no assertion criteria provided	Pathogenic (Dec 13, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000840362

OMIM

no assertion criteria provided

Pathogenic
(Dec 13, 2018)

germline

literature only

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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Bi-allelic Mutations in NDUFA6 Establish Its Role in Early-Onset Isolated Mitochondrial Complex I Deficiency.

Alston CL, Heidler J, Dibley MG, Kremer LS, Taylor LS, Fratter C, French CE, Glasgow RIC, Feichtinger RG, Delon I, Pagnamenta AT, Dolling H, Lemonde H, Aiton N, Bjørnstad A, Henneke L, Gärtner J, Thiele H, Tauchmannova K, Quaghebeur G, Houstek J, Sperl W, et al.

Am J Hum Genet. 2018 Oct 4;103(4):592-601. doi: 10.1016/j.ajhg.2018.08.013. Epub 2018 Sep 20.

PubMed [citation]

PMID:: 30245030
PMCID:: PMC6174280

Details of each submission

From OMIM, SCV000840362.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a female infant, born of unrelated Hungarian parents (family 1), with lethal mitochondrial complex I deficiency nuclear type 33 (MC1DN33; 618253), Alston et al. (2018) identified compound heterozygous mutations in the NDUFA6 gene: a c.191G-C transversion (c.191G-C, NM_002490.5), resulting in an arg64-to-pro (R64P) substitution, and a c.265G-T transversion, resulting in a glu89-to-ter (E89X; 602138.0002) substitution. The mutations, which were found by a panel-based targeted capture, segregated with the disorder in the family. The E89X variant had a minor allele frequency of 0.0008% in the gnomAD database. Patient cells showed a marked reduction in fully assembled complex I, as well as a marked impairment in cell respiration and decreased complex I activity (44% of controls). These defects could be rescued by expression of wildtype NDUFA6. The patient presented at birth with intrauterine growth retardation, respiratory insufficiency, lactic acidosis, and hypoglycemia. She also had abnormal clotting and died at 51 hours of age.

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

Last Updated: Dec 9, 2023

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