NM_015915.5(ATL1):c.1213G>A (p.Val405Met) AND Hereditary spastic paraplegia 3A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 20, 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:: RCV000530204.7

Allele description [Variation Report for NM_015915.5(ATL1):c.1213G>A (p.Val405Met)]

NM_015915.5(ATL1):c.1213G>A (p.Val405Met)

Gene:

ATL1:atlastin GTPase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q22.1

Genomic location:

Preferred name:

NM_015915.5(ATL1):c.1213G>A (p.Val405Met)

HGVS:

NC_000014.9:g.50628124G>A
NG_009028.1:g.100043G>A
NM_001127713.1:c.1213G>A
NM_015915.5:c.1213G>AMANE SELECT
NM_181598.4:c.1213G>A
NP_001121185.1:p.Val405Met
NP_056999.2:p.Val405Met
NP_056999.2:p.Val405Met
NP_853629.2:p.Val405Met
LRG_360t1:c.1213G>A
LRG_360t2:c.1213G>A
LRG_360:g.100043G>A
LRG_360p1:p.Val405Met
LRG_360p2:p.Val405Met
NC_000014.8:g.51094842G>A
NM_015915.4:c.1213G>A

Protein change:

V405M

Links:

dbSNP: rs201240362

NCBI 1000 Genomes Browser:

rs201240362

Molecular consequence:

NM_001127713.1:c.1213G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015915.5:c.1213G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181598.4:c.1213G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary spastic paraplegia 3A (SPG3A)
Synonyms:: SPASTIC PARAPLEGIA 3, AUTOSOMAL DOMINANT; FAMILIAL SPASTIC PARAPLEGIA, AUTOSOMAL DOMINANT, 1; SPG3; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008437; MedGen: C2931355; Orphanet: 100984; OMIM: 182600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000649534	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 20, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31594988, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000649534

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 20, 2023)

germline

clinical testing

PubMed (2)
[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

Mutational Spectrum of Spast (Spg4) and Atl1 (Spg3a) Genes In Russian Patients With Hereditary Spastic Paraplegia.

Kadnikova VA, Rudenskaya GE, Stepanova AA, Sermyagina IG, Ryzhkova OP.

Sci Rep. 2019 Oct 8;9(1):14412. doi: 10.1038/s41598-019-50911-9.

PubMed [citation]

PMID:: 31594988
PMCID:: PMC6783457

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, SCV000649534.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is present in population databases (rs201240362, gnomAD 0.008%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATL1 protein function. ClinVar contains an entry for this variant (Variation ID: 471245). This missense change has been observed in individual(s) with autosomal dominant hereditary spastic paraplegia (PMID: 31594988). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 405 of the ATL1 protein (p.Val405Met).

#	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: Nov 3, 2024

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