NM_213720.3(CHCHD10):c.67C>A (p.Pro23Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 15, 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:: RCV003064644.2

Allele description [Variation Report for NM_213720.3(CHCHD10):c.67C>A (p.Pro23Thr)]

NM_213720.3(CHCHD10):c.67C>A (p.Pro23Thr)

Gene:

CHCHD10:coiled-coil-helix-coiled-coil-helix domain containing 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.23

Genomic location:

Preferred name:

NM_213720.3(CHCHD10):c.67C>A (p.Pro23Thr)

HGVS:

NC_000022.11:g.23767568G>T
NG_034223.1:g.5405C>A
NM_001301339.2:c.67C>A
NM_213720.1:c.67C>A
NM_213720.3:c.67C>AMANE SELECT
NP_001288268.1:p.Pro23Thr
NP_998885.1:p.Pro23Thr
NC_000022.10:g.24109755G>T

Protein change:

P23T

Molecular consequence:

NM_001301339.2:c.67C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_213720.3:c.67C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lower motor neuron syndrome with late-adult onset (SMAJ)
Synonyms:: Spinal muscular atrophy, Jokela type
Identifiers:: MONDO: MONDO:0014025; MedGen: C3554398; Orphanet: 276435; OMIM: 615048

Name:: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2
Synonyms:: FTDALS2
Identifiers:: MONDO: MONDO:0014395; MedGen: C4014648; Orphanet: 275872; OMIM: 615911

Name:: Autosomal dominant mitochondrial myopathy with exercise intolerance (IMMD)
Synonyms:: Myopathy, isolated mitochondrial, autosomal dominant
Identifiers:: MONDO: MONDO:0014532; MedGen: C4015513; Orphanet: 457050; OMIM: 616209

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003444370	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 15, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29789341, 25833818, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003444370

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 15, 2022)

germline

clinical testing

PubMed (3)
[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

A novel CHCHD10 mutation implicates a Mia40-dependent mitochondrial import deficit in ALS.

Lehmer C, Schludi MH, Ransom L, Greiling J, Junghänel M, Exner N, Riemenschneider H, van der Zee J, Van Broeckhoven C, Weydt P, Heneka MT, Edbauer D.

EMBO Mol Med. 2018 Jun;10(6). doi:pii: e8558. 10.15252/emmm.201708558.

PubMed [citation]

PMID:: 29789341
PMCID:: PMC5991575

Mutation analysis of CHCHD10 in different neurodegenerative diseases.

Zhang M, Xi Z, Zinman L, Bruni AC, Maletta RG, Curcio SA, Rainero I, Rubino E, Pinessi L, Nacmias B, Sorbi S, Galimberti D, Lang AE, Fox S, Surace EI, Ghani M, Guo J, Sato C, Moreno D, Liang Y, Keith J, Traynor BJ, et al.

Brain. 2015 Sep;138(Pt 9):e380. doi: 10.1093/brain/awv082. Epub 2015 Mar 31. No abstract available.

PubMed [citation]

PMID:: 25833818
PMCID:: PMC4547051

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003444370.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 23 of the CHCHD10 protein (p.Pro23Thr). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not substantially affect CHCHD10 function (PMID: 29789341). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with frontotemporal lobar degeneration (PMID: 25833818). This variant is not present in population databases (gnomAD no frequency).

#	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: May 1, 2024

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