VCV000021528.4 - ClinVar

NM_015915.5(ATL1):c.1519dup (p.Ile507fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(3)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Pathogenic(2); Uncertain significance(1)

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_015915.5(ATL1):c.1519dup (p.Ile507fs)

Variation ID: 21528 Accession: VCV000021528.4

Type and length

Duplication, 1 bp

Location

Cytogenetic: 14q22.1 14: 50628428-50628429 (GRCh38) [ NCBI UCSC ] 14: 51095146-51095147 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Jul 16, 2023	Jan 6, 2016

HGVS

Nucleotide	Protein	Molecular consequence
NM_015915.5:c.1519dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_056999.2:p.Ile507fs	frameshift
NM_001127713.1:c.1519dup	NP_001121185.1:p.Ile507fs	frameshift
NM_015915.4:c.1519dupA
NM_181598.4:c.1519dup	NP_853629.2:p.Ile507fs	frameshift
NC_000014.9:g.50628430dup
NC_000014.8:g.51095148dup
NG_009028.1:g.100349dup
LRG_360:g.100349dup
LRG_360t1:c.1519dup
LRG_360t2:c.1519dup	LRG_360p2:p.Ile507fs
	NP_001121185.1:p.Ile507Asnfs
	NP_056999.2:p.Ile507Asnfs

... more HGVS ... less HGVS

Protein change

I507fs

Other names

AY032844.1:n.1688dup

Canonical SPDI

NC_000014.9:50628428:AA:AAA

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA342177 OMIM: 606439.0005 dbSNP: rs863223314 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ATL1		-	-	GRCh38 GRCh37	558	595

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Hereditary spastic paraplegia 3A	Conflicting interpretations of pathogenicity (3)	no assertion criteria provided	Jan 6, 2016	RCV000020718.5

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Dec 24, 2002)	no assertion criteria provided Method: literature only	SPASTIC PARAPLEGIA 3, AUTOSOMAL DOMINANT Affected status: not provided Allele origin: germline	OMIM Accession: SCV000024772.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (1) PubMed: 12499504 Comment on evidence: In an Italian family with autosomal dominant hereditary spastic paraplegia (182600), Tessa et al. (2002) identified a heterozygous 1-bp insertion, 1688A, in exon 12 of … (more) In an Italian family with autosomal dominant hereditary spastic paraplegia (182600), Tessa et al. (2002) identified a heterozygous 1-bp insertion, 1688A, in exon 12 of the ATL1 gene, producing a frameshift and premature stop codon. The resulting protein lacked the last 37 amino acids, including all of exon 14. Seven clearly affected individuals and 2 asymptomatic individuals with hyperreflexia carried the mutation. The authors commented on the apparent age-dependent penetrance of the disorder in this family. (less)
pathologic (Sep 21, 2010)	no assertion criteria provided Method: curation	Spastic Paraplegia 3A Affected status: not provided Allele origin: not provided	GeneReviews Accession: SCV000041288.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Comment: Converted during submission to Pathogenic.
Uncertain significance (Jan 06, 2016)	no assertion criteria provided Method: literature only	Hereditary spastic paraplegia 3A Affected status: yes Allele origin: germline	Inherited Neuropathy Consortium Ii, University Of Miami Accession: SCV004011948.1 First in ClinVar: Jul 16, 2023 Last updated: Jul 16, 2023	Publications: PubMed (1) PubMed: 24002164

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Spastic Paraplegia 3A.	Adam MP	-	2020	PMID: 20862796
Occipital horn syndrome and classical Menkes Syndrome caused by deep intronic mutations, leading to the activation of ATP7A pseudo-exon.	Yasmeen S	European journal of human genetics : EJHG	2014	PMID: 24002164
SPG3A: An additional family carrying a new atlastin mutation.	Tessa A	Neurology	2002	PMID: 12499504

Text-mined citations for rs863223314 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Feb 04, 2024

ClinVar Genomic variation as it relates to human health

NM_015915.5(ATL1):c.1519dup (p.Ile507fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs863223314 ...