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NM_014231.5(VAMP1):c.340del (p.Ile114fs) AND Spastic ataxia 1

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 10, 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:
RCV002279727.2

Allele description [Variation Report for NM_014231.5(VAMP1):c.340del (p.Ile114fs)]

NM_014231.5(VAMP1):c.340del (p.Ile114fs)

Genes:
TAPBPL:TAP binding protein like [Gene - OMIM - HGNC]
VAMP1:vesicle associated membrane protein 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
12p13.31
Genomic location:
Preferred name:
NM_014231.5(VAMP1):c.340del (p.Ile114fs)
HGVS:
  • NC_000012.12:g.6464891del
  • NG_042188.2:g.11010del
  • NM_001297438.2:c.340del
  • NM_014231.5:c.340delMANE SELECT
  • NM_016830.4:c.340del
  • NM_199245.3:c.340del
  • NP_001284367.1:p.Arg114fs
  • NP_055046.1:p.Ile114fs
  • NP_058439.1:p.Arg114fs
  • NP_954740.1:p.Ser114fs
  • NC_000012.11:g.6574057del
  • NG_042188.1:g.11010del
  • NM_014231.3:c.340del
  • NM_014231.3:c.340delA
  • NM_014231.4:c.340del
  • NM_014231.5:c.340delAMANE SELECT
  • NR_123717.2:n.359del
Protein change:
I114fs
Links:
OMIM: 185880.0002; dbSNP: rs746220436
NCBI 1000 Genomes Browser:
rs746220436
Molecular consequence:
  • NM_001297438.2:c.340del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014231.5:c.340del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_016830.4:c.340del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_199245.3:c.340del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_123717.2:n.359del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Spastic ataxia 1
Synonyms:
Ataxia, spastic, 1, autosomal dominant
Identifiers:
MONDO: MONDO:0007164; MedGen: C1970107; Orphanet: 251282; OMIM: 108600

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002567978DASA
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Aug 10, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Novel synaptobrevin-1 mutation causes fatal congenital myasthenic syndrome.

Shen XM, Scola RH, Lorenzoni PJ, Kay CS, Werneck LC, Brengman J, Selcen D, Engel AG.

Ann Clin Transl Neurol. 2017 Feb;4(2):130-138. doi: 10.1002/acn3.387. Erratum in: Ann Clin Transl Neurol. 2017 May 08;4(5):356. doi: 10.1002/acn3.422.

PubMed [citation]
PMID:
28168212
PMCID:
PMC5288468

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

Details of each submission

From DASA, SCV002567978.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The c.340del;p.(Ile114Serfs*72) is a null frameshift variant (NMD) in the VAMP1 gene without sufficient information about prediction of nonsense mediated mRNA decay (NMD); it is present in a relevant exon to the transcript, and disrupts < 10% of the protein product – PVS1_moderate. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant(ClinVar ID: 619001; PMID: 28168212) - PS4_supporting. The variant is present at low allele frequencies population databases (rs746220436 – gnomAD 0.0001314%; ABraOM no frequency - https://abraom.ib.usp.br/) -PM2_supporting.The p.(Ile114Serfs*72) was detected in trans with a pathogenic variant (PMID:28168212) - PM3. In summary, the currently available evidence indicates that the variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 26, 2024