NM_015915.5(ATL1):c.1546G>A (p.Asp516Asn) AND Hereditary spastic paraplegia 3A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 2018
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:: RCV000696450.7

Allele description [Variation Report for NM_015915.5(ATL1):c.1546G>A (p.Asp516Asn)]

NM_015915.5(ATL1):c.1546G>A (p.Asp516Asn)

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.1546G>A (p.Asp516Asn)

HGVS:

NC_000014.9:g.50628457G>A
NG_009028.1:g.100376G>A
NM_001127713.1:c.1546G>A
NM_015915.5:c.1546G>AMANE SELECT
NM_181598.4:c.1546G>A
NP_001121185.1:p.Asp516Asn
NP_056999.2:p.Asp516Asn
NP_056999.2:p.Asp516Asn
NP_853629.2:p.Asp516Asn
LRG_360t1:c.1546G>A
LRG_360t2:c.1546G>A
LRG_360:g.100376G>A
LRG_360p1:p.Asp516Asn
LRG_360p2:p.Asp516Asn
NC_000014.8:g.51095175G>A
NM_015915.4:c.1546G>A

Protein change:

D516N

Links:

dbSNP: rs776441162

NCBI 1000 Genomes Browser:

rs776441162

Molecular consequence:

NM_001127713.1:c.1546G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015915.5:c.1546G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181598.4:c.1546G>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
SCV000825013	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 22, 2018)	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

SCV000825013

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 22, 2018)

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, SCV000825013.4

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

Description

This variant has not been reported in the literature in individuals with ATL1-related disease. This sequence change replaces aspartic acid with asparagine at codon 516 of the ATL1 protein (p.Asp516Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs776441162, ExAC 0.002%). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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