NM_015346.4(ZFYVE26):c.4312C>T (p.Arg1438Ter) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV001035676.7

Allele description [Variation Report for NM_015346.4(ZFYVE26):c.4312C>T (p.Arg1438Ter)]

NM_015346.4(ZFYVE26):c.4312C>T (p.Arg1438Ter)

Gene:

ZFYVE26:zinc finger FYVE-type containing 26 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.1

Genomic location:

Preferred name:

NM_015346.4(ZFYVE26):c.4312C>T (p.Arg1438Ter)

HGVS:

NC_000014.9:g.67782840G>A
NG_011836.1:g.38750C>T
NM_015346.4:c.4312C>TMANE SELECT
NP_056161.2:p.Arg1438Ter
NC_000014.8:g.68249557G>A
NM_015346.3:c.4312C>T

Protein change:

R1438*; ARG1438TER

Links:

OMIM: 612012.0001; dbSNP: rs118204049

NCBI 1000 Genomes Browser:

rs118204049

Molecular consequence:

NM_015346.4:c.4312C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Spastic paraplegia
Identifiers:: MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001199010	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19805727, 18394578, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001199010

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

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

SPG15 is the second most common cause of hereditary spastic paraplegia with thin corpus callosum.

Goizet C, Boukhris A, Maltete D, Guyant-Maréchal L, Truchetto J, Mundwiller E, Hanein S, Jonveaux P, Roelens F, Loureiro J, Godet E, Forlani S, Melki J, Auer-Grumbach M, Fernandez JC, Martin-Hardy P, Sibon I, Sole G, Orignac I, Mhiri C, Coutinho P, Durr A, et al.

Neurology. 2009 Oct 6;73(14):1111-9. doi: 10.1212/WNL.0b013e3181bacf59.

PubMed [citation]

PMID:: 19805727

Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome.

Hanein S, Martin E, Boukhris A, Byrne P, Goizet C, Hamri A, Benomar A, Lossos A, Denora P, Fernandez J, Elleuch N, Forlani S, Durr A, Feki I, Hutchinson M, Santorelli FM, Mhiri C, Brice A, Stevanin G.

Am J Hum Genet. 2008 Apr;82(4):992-1002. doi: 10.1016/j.ajhg.2008.03.004.

PubMed [citation]

PMID:: 18394578
PMCID:: PMC2427184

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001199010.5

#	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 creates a premature translational stop signal (p.Arg1438*) in the ZFYVE26 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZFYVE26 are known to be pathogenic (PMID: 18394578, 19805727). This variant is present in population databases (rs118204049, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 18394578). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 749). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 16, 2024

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