NM_014946.4(SPAST):c.120_121delinsAA (p.Pro41Thr) AND Hereditary spastic paraplegia 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 9, 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:: RCV003869650.2

Allele description [Variation Report for NM_014946.4(SPAST):c.120_121delinsAA (p.Pro41Thr)]

NM_014946.4(SPAST):c.120_121delinsAA (p.Pro41Thr)

Gene:

SPAST:spastin [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

2p22.3

Genomic location:

Preferred name:

NM_014946.4(SPAST):c.120_121delinsAA (p.Pro41Thr)

HGVS:

NC_000002.12:g.32063951_32063952delinsAA
NG_008730.1:g.5341_5342delinsAA
NG_094904.1:g.584_585delinsAA
NM_001363823.2:c.120_121delinsAA
NM_001363875.2:c.120_121delinsAA
NM_001377959.1:c.120_121delinsAA
NM_014946.4:c.120_121delinsAAMANE SELECT
NM_199436.2:c.120_121delinsAA
NP_001350752.1:p.Pro41Thr
NP_001350804.1:p.Pro41Thr
NP_001364888.1:p.Pro41Thr
NP_055761.2:p.Pro41Thr
NP_055761.2:p.Pro41Thr
NP_955468.1:p.Pro41Thr
LRG_714t1:c.120_121delTCinsAA
LRG_714:g.5341_5342delinsAA
LRG_714p1:p.Pro41Thr
NC_000002.11:g.32289020_32289021delinsAA
NM_014946.3:c.120_121delTCinsAA

Protein change:

P41T

Molecular consequence:

NM_001363823.2:c.120_121delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001363875.2:c.120_121delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001377959.1:c.120_121delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_014946.4:c.120_121delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_199436.2:c.120_121delinsAA - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary spastic paraplegia 4
Synonyms:: Spastic paraplegia 4, autosomal dominant; Familial spastic paraplegia autosomal dominant 2
Identifiers:: MONDO: MONDO:0008438; MedGen: C1866855; Orphanet: 100985; OMIM: 182601

Recent activity

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Mus musculus calcium binding protein 7 (Cabp7), mRNA
Mus musculus calcium binding protein 7 (Cabp7), mRNA
gi|1690553864|ref|NM_138948.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004673188	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004673188

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 9, 2024)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004673188.1

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

Description

This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 41 of the SPAST protein (p.Pro41Thr). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with SPAST-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

#	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 29, 2024

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