TOMM7

protein-coding

translocase of outer mitochondrial membrane 7, the group of Translocase of outer mitochondrial membrane complex

Gene summary

This gene encodes a subunit of the translocase of the outer mitochondrial membrane. The encoded protein regulates the assembly and stability of the translocase complex. [provided by RefSeq, Oct 2012]

MANE transcript

NM_019059.5

Inheritance

ClinVar variants

P:3U:10

Top phenotype

Garg-Mishra progeroid syndrome

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr7:22,812,628-22,822,849

External References & Databases

Ensembl (ENSG00000196683)

Transcript & Mutation Effects

hg38 • Region Span ~10.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Garg-Mishra progeroid syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957953

Submitter: Ambry Genetics

Garg-Mishra progeroid syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0957953

Submitter: Ambry Genetics

Garg-Mishra progeroid syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957953

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Garg-Mishra progeroid syndromeAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 36282599; 36299998

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TOMM7 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 10

Garg-Mishra progeroid syndromeTotal: 2

TOMM7-related early onset Leigh diseaseTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019059.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense	1 clinvar	1 clinvar	8 clinvar			10
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	1	10	0	0	13

Highest pathogenic variant AF is 0.000008055232

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019059.5	RefSeq	NP_061932.1	3	MANE Select
ENST00000358435.9	Ensembl	ENSP00000351214.4	3	MANE Select
ENST00000372879.8	Ensembl	ENSP00000361970.4	4	Standard
ENST00000372879.9	Ensembl	ENSP00000361970.4	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mitophagy - animal - Homo sapiens (human)
Metabolism of proteins
Pink/Parkin Mediated Mitophagy
Mitophagy
Mitochondrial protein import

Biological Process

protein targeting to mitochondrion
protein import into mitochondrial matrix
regulation of protein stability
positive regulation of mitophagy in response to mitochondrial depolarization
positive regulation of protein targeting to mitochondrion

Molecular Function

protein binding
protein transmembrane transporter activity

Cellular Component

mitochondrion
mitochondrial outer membrane
mitochondrial outer membrane translocase complex
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358435
Coding exons: 3
Length: 10220
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125747
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.153	31	28.7	1.08	0.00000130	353
Missense (PolyPhen)		5	5.2373	0.95469		68
Synonymous	-1.96	18	10.1	1.79	5.16e-7	102
Loss of Function	0.336	3	3.70	0.811	1.57e-7	40

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for assembly and stability of the TOM complex. Positive regulator of PRKN translocation to damaged mitochondria. Acts probably by stabilizing PINK1 on the outer membrane of depolarized mitochondria. {ECO:0000269|PubMed:18331822, ECO:0000269|PubMed:24270810}.;

Intolerance Scores

LoFtool: 0.474
RVIS EVS: -0.01
RVIS percentile EVS: 52.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0314

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium