NM_015915.5(ATL1):c.1243C>T (p.Arg415Trp) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Feb 1, 2024
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:: RCV001090532.30

Allele description [Variation Report for NM_015915.5(ATL1):c.1243C>T (p.Arg415Trp)]

NM_015915.5(ATL1):c.1243C>T (p.Arg415Trp)

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.1243C>T (p.Arg415Trp)

HGVS:

NC_000014.9:g.50628154C>T
NG_009028.1:g.100073C>T
NM_001127713.1:c.1243C>T
NM_015915.5:c.1243C>TMANE SELECT
NM_181598.4:c.1243C>T
NP_001121185.1:p.Arg415Trp
NP_056999.2:p.Arg415Trp
NP_056999.2:p.Arg415Trp
NP_853629.2:p.Arg415Trp
LRG_360t1:c.1243C>T
LRG_360t2:c.1243C>T
LRG_360:g.100073C>T
LRG_360p1:p.Arg415Trp
LRG_360p2:p.Arg415Trp
NC_000014.8:g.51094872C>T
NM_015915.3:c.1243C>T
NM_015915.4:c.1243C>T
Q8WXF7:p.Arg415Trp

Protein change:

R415W; ARG415TRP

Links:

UniProtKB: Q8WXF7#VAR_065512; OMIM: 606439.0007; dbSNP: rs119476050

NCBI 1000 Genomes Browser:

rs119476050

Molecular consequence:

NM_001127713.1:c.1243C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015915.5:c.1243C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_181598.4:c.1243C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV001246136	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Feb 1, 2024)	germline	clinical testing	Citation Link,
SCV001446483	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001716182	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 10, 2020)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 15184642, 23483706, 24417445, 30780198, 20932283, 26671083, 25741868
SCV003837298	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Sep 13, 2022)	germline	clinical testing	Citation Link,
SCV004229184	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely pathogenic (Jun 7, 2023)	unknown	clinical testing	PubMed (12) [See all records that cite these PMIDs] 20932283, 23483706, 30780198, 26671083, 24451228, 15184642, 4684346, 31594988, 27108959, 27217339, 24417445, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	6	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia.

Alvarez V, Sánchez-Ferrero E, Beetz C, Díaz M, Alonso B, Corao AI, Gámez J, Esteban J, Gonzalo JF, Pascual-Pascual SI, López de Munain A, Moris G, Ribacoba R, Márquez C, Rosell J, Marín R, García-Barcina MJ, Del Castillo E, Benito C, Coto E; Group for the Study of the Genetics of Spastic Paraplegia..

BMC Neurol. 2010 Oct 8;10:89. doi: 10.1186/1471-2377-10-89.

PubMed [citation]

PMID:: 20932283
PMCID:: PMC2964648

See all PubMed Citations (13)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001246136.24

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	not provided

Description

ATL1: PP1:Strong, PM1, PM2, PM5, PS4:Moderate, PP3

#	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		6	not provided	not provided	not provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446483.1

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001716182.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

Description

PS4_moderate, PM1, PM2, PP3

#	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		1	not provided	not provided	not provided

From GeneDx, SCV003837298.1

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

Description

Reported previously in a large multi-generation family with early onset progressive spastic paraplegia in affected and unaffected individuals suggesting of autosomal dominant inheritance with reduced penetrance (D'Amico et al., 2004); 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: 23334294, 31594988, 24417445, 30780198, 26671083, 20862796, 21220294, 34808209, 20932283, 25341883, 31236401, 15184642, 23483706)

#	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, SCV004229184.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with autosomal dominant spastic paraplegia. Computational tools predict that this variant is damaging.

#	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

Last Updated: Aug 4, 2024

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