NM_025137.4(SPG11):c.5381T>C (p.Leu1794Pro) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 9, 2023
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:: RCV003168606.4

Allele description [Variation Report for NM_025137.4(SPG11):c.5381T>C (p.Leu1794Pro)]

NM_025137.4(SPG11):c.5381T>C (p.Leu1794Pro)

Gene:

SPG11:SPG11 vesicle trafficking associated, spatacsin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_025137.4(SPG11):c.5381T>C (p.Leu1794Pro)

HGVS:

NC_000015.10:g.44584299A>G
NG_008885.1:g.84380T>C
NM_001160227.2:c.5381T>C
NM_025137.4:c.5381T>CMANE SELECT
NP_001153699.1:p.Leu1794Pro
NP_079413.3:p.Leu1794Pro
NC_000015.9:g.44876497A>G
NM_025137.3:c.5381T>C

Protein change:

L1794P

Links:

dbSNP: rs201689565

NCBI 1000 Genomes Browser:

rs201689565

Molecular consequence:

NM_001160227.2:c.5381T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_025137.4:c.5381T>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

unknown functional consequence

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003871801	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 9, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 26374131, 27790088, 31407473, 33098801, 35254204, 36139378 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003871801

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 9, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

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

Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing.

Lynch DS, Koutsis G, Tucci A, Panas M, Baklou M, Breza M, Karadima G, Houlden H.

Eur J Hum Genet. 2016 Jun;24(6):857-63. doi: 10.1038/ejhg.2015.200. Epub 2015 Sep 16.

PubMed [citation]

PMID:: 26374131
PMCID:: PMC4688955

Rare Variants in Neurodegeneration Associated Genes Revealed by Targeted Panel Sequencing in a German ALS Cohort.

Krüger S, Battke F, Sprecher A, Munz M, Synofzik M, Schöls L, Gasser T, Grehl T, Prudlo J, Biskup S.

Front Mol Neurosci. 2016;9:92.

PubMed [citation]

PMID:: 27790088
PMCID:: PMC5061735

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV003871801.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The c.5381T>C (p.L1794P) alteration is located in exon 30 (coding exon 30) of the SPG11 gene. This alteration results from a T to C substitution at nucleotide position 5381, causing the leucine (L) at amino acid position 1794 to be replaced by a proline (P). Based on data from gnomAD, the C allele has an overall frequency of 0.006% (16/281906) total alleles studied. The highest observed frequency was 0.012% (15/128650) of European (non-Finnish) alleles. This mutation has been reported in the homozygous and compound heterozygous state in individuals with spastic paraplegia (Lynch, 2015; Krenn, 2020; Doleckova, 2022; Peri, 2022). It was also identified in the homozygous state in an individual with childhood-onset dystonia (Zech, 2020) and in the heterozygous state in an individual with amyotrophic lateral sclerosis with no second SPG11 variant (Krüger, 2016). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is 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: Sep 8, 2024

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