NM_015915.5(ATL1):c.1226G>A (p.Gly409Asp) AND Hereditary spastic paraplegia 3A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 26, 2022
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:: RCV003502587.2

Allele description [Variation Report for NM_015915.5(ATL1):c.1226G>A (p.Gly409Asp)]

NM_015915.5(ATL1):c.1226G>A (p.Gly409Asp)

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.1226G>A (p.Gly409Asp)

HGVS:

NC_000014.9:g.50628137G>A
NG_009028.1:g.100056G>A
NM_001127713.1:c.1226G>A
NM_015915.5:c.1226G>AMANE SELECT
NM_181598.4:c.1226G>A
NP_001121185.1:p.Gly409Asp
NP_056999.2:p.Gly409Asp
NP_853629.2:p.Gly409Asp
LRG_360t1:c.1226G>A
LRG_360t2:c.1226G>A
LRG_360:g.100056G>A
LRG_360p2:p.Gly409Asp
NC_000014.8:g.51094855G>A
NC_000014.8:g.51094855G>A
NM_015915.4:c.1226G>A

Protein change:

G409D

Links:

dbSNP: rs2039539644

NCBI 1000 Genomes Browser:

rs2039539644

Molecular consequence:

NM_001127713.1:c.1226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015915.5:c.1226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181598.4:c.1226G>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

Recent activity

Clear Turn Off Turn On

Model organism or animal sample from Macaca assamensis
Model organism or animal sample from Macaca assamensis

biosample
olfactory receptor 1L3 [Homo sapiens]
olfactory receptor 1L3 [Homo sapiens]
gi|52546685|ref|NP_001005234.1|

Protein
LOC127404042 [Homo sapiens]
LOC127404042 [Homo sapiens]
Gene ID:127404042

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004297095	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 26, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25193411, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297095

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 26, 2022)

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

Extremely severe complicated spastic paraplegia 3A with neonatal onset.

Yonekawa T, Oya Y, Higuchi Y, Hashiguchi A, Takashima H, Sugai K, Sasaki M.

Pediatr Neurol. 2014 Nov;51(5):726-9. doi: 10.1016/j.pediatrneurol.2014.07.027. Epub 2014 Jul 24.

PubMed [citation]

PMID:: 25193411

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, SCV004297095.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly409 amino acid residue in ATL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt ATL1 protein function. ClinVar contains an entry for this variant (Variation ID: 870859). This missense change has been observed in individual(s) with spastic paraplegia (PMID: 25193411). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 409 of the ATL1 protein (p.Gly409Asp).

#	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: Oct 8, 2024

ClinVar

Relating variation to medicine