NM_015915.5(ATL1):c.1483C>T (p.Arg495Trp) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 23, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000390284.16

Allele description [Variation Report for NM_015915.5(ATL1):c.1483C>T (p.Arg495Trp)]

NM_015915.5(ATL1):c.1483C>T (p.Arg495Trp)

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.1483C>T (p.Arg495Trp)

HGVS:

NC_000014.9:g.50628394C>T
NG_009028.1:g.100313C>T
NM_001127713.1:c.1483C>T
NM_015915.5:c.1483C>TMANE SELECT
NM_181598.4:c.1483C>T
NP_001121185.1:p.Arg495Trp
NP_056999.2:p.Arg495Trp
NP_056999.2:p.Arg495Trp
NP_853629.2:p.Arg495Trp
LRG_360t1:c.1483C>T
LRG_360t2:c.1483C>T
LRG_360:g.100313C>T
LRG_360p1:p.Arg495Trp
LRG_360p2:p.Arg495Trp
NC_000014.8:g.51095112C>T
NM_001127713.1:c.1483C>T
NM_015915.4:c.1483C>T
Q8WXF7:p.Arg495Trp

Protein change:

R495W

Links:

UniProtKB: Q8WXF7#VAR_067660; dbSNP: rs864622269

NCBI 1000 Genomes Browser:

rs864622269

Molecular consequence:

NM_001127713.1:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015915.5:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_181598.4:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329929	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 23, 2023)	germline	clinical testing	Citation Link,
SCV001475555	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Jul 15, 2020)	unknown	clinical testing	PubMed (15) [See all records that cite these PMIDs] 17321752, 17502470, 20932283, 20718791, 23079343, 20816793, 32322428, 26374131, 30780198, 31920481, 15742100, 26208798, 23400676, 15596607, 26467025
SCV001480099	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2021)	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

SCV000329929

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 23, 2023)

germline

clinical testing

Citation Link,

SCV001475555

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Jul 15, 2020)

unknown

clinical testing

PubMed (15)
[See all records that cite these PMIDs]

SCV001480099

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 1, 2021)

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	yes	not provided	not provided	not provided	1	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis.

Namekawa M, Muriel MP, Janer A, Latouche M, Dauphin A, Debeir T, Martin E, Duyckaerts C, Prigent A, Depienne C, Sittler A, Brice A, Ruberg M.

Mol Cell Neurosci. 2007 May;35(1):1-13. Epub 2007 Jan 26.

PubMed [citation]

PMID:: 17321752

Hereditary spastic paraplegia 3A associated with axonal neuropathy.

Ivanova N, Claeys KG, Deconinck T, Litvinenko I, Jordanova A, Auer-Grumbach M, Haberlova J, Löfgren A, Smeyers G, Nelis E, Mercelis R, Plecko B, Priller J, Zámecník J, Ceulemans B, Erichsen AK, Björck E, Nicholson G, Sereda MW, Seeman P, Kremensky I, Mitev V, et al.

Arch Neurol. 2007 May;64(5):706-13.

PubMed [citation]

PMID:: 17502470

See all PubMed Citations (16)

Details of each submission

From GeneDx, SCV000329929.8

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

Description

Published functional studies suggest a dominant-negative effect on the BMPRII signaling pathway (Zhao et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26208798, 20816793, 23079343, 22266886, 20932283, 16815977, 17321752, 15596607, 26374131, 26671083, 20718791, 24451228, 17502470, 15742100, 31236401, 30780198, 35925862, 31920481, 32322428, 23400676, 35788923, 34788679, 23334294, 36359747)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV001475555.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (15)

Description

The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. Found in multiple unrelated patients with expected phenotype for this gene. Assessment of experimental evidence regarding the effect of this variant on protein function is inconclusive. Statistically associated with disease in multiple families.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001480099.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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