NM_015046.7(SETX):c.4903T>A (p.Leu1635Met) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 27, 2020
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:: RCV000545900.6

Allele description [Variation Report for NM_015046.7(SETX):c.4903T>A (p.Leu1635Met)]

NM_015046.7(SETX):c.4903T>A (p.Leu1635Met)

Gene:

SETX:senataxin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.13

Genomic location:

Preferred name:

NM_015046.7(SETX):c.4903T>A (p.Leu1635Met)

HGVS:

NC_000009.12:g.132326695A>T
NG_007946.1:g.33291T>A
NM_001351527.2:c.4903T>A
NM_001351528.2:c.4903T>A
NM_015046.7:c.4903T>AMANE SELECT
NP_001338456.1:p.Leu1635Met
NP_001338457.1:p.Leu1635Met
NP_055861.3:p.Leu1635Met
LRG_268t1:c.4903T>A
LRG_268:g.33291T>A
NC_000009.11:g.135202082A>T
NM_015046.5:c.4903T>A

Protein change:

L1635M

Links:

dbSNP: rs1466879487

NCBI 1000 Genomes Browser:

rs1466879487

Molecular consequence:

NM_001351527.2:c.4903T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351528.2:c.4903T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015046.7:c.4903T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Amyotrophic lateral sclerosis type 4 (ALS4)
Synonyms:: AMYOTROPHIC LATERAL SCLEROSIS 4, JUVENILE; NEURONOPATHY, DISTAL HEREDITARY MOTOR, WITH PYRAMIDAL FEATURES
Identifiers:: MONDO: MONDO:0011223; MedGen: C1865409; Orphanet: 357043; OMIM: 602433

Name:: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (SCAN2)
Synonyms:: Ataxia-oculomotor apraxia 2; Ataxia-ocular apraxia-2; Ataxia with Oculomotor Apraxia
Identifiers:: MONDO: MONDO:0018996; MedGen: C1853761; Orphanet: 64753; OMIM: 606002

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000645270	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 27, 2020)	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

SCV000645270

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 27, 2020)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000645270.4

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

Description

In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SETX-related disease. This sequence change replaces leucine with methionine at codon 1635 of the SETX protein (p.Leu1635Met). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and methionine.

#	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 5, 2024

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