NM_006178.4(NSF):c.1688C>T (p.Pro563Leu) AND Developmental and epileptic encephalopathy 96

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 10, 2023
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:: RCV001449912.3

Allele description [Variation Report for NM_006178.4(NSF):c.1688C>T (p.Pro563Leu)]

NM_006178.4(NSF):c.1688C>T (p.Pro563Leu)

Genes:

NSF:N-ethylmaleimide sensitive factor, vesicle fusing ATPase [Gene - OMIM - HGNC]
LRRC37A2:leucine rich repeat containing 37 member A2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_006178.4(NSF):c.1688C>T (p.Pro563Leu)

HGVS:

NC_000017.11:g.46713913C>T
NM_006178.4:c.1688C>TMANE SELECT
NP_006169.2:p.Pro563Leu
NC_000017.10:g.44791279C>T
NM_006178.3:c.1688C>T
NR_040116.2:n.1755C>T

Protein change:

P563L; PRO563LEU

Links:

OMIM: 601633.0002; dbSNP: rs2146266663

NCBI 1000 Genomes Browser:

rs2146266663

Molecular consequence:

NM_006178.4:c.1688C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_040116.2:n.1755C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Developmental and epileptic encephalopathy 96
Identifiers:: MONDO: MONDO:0023659; MedGen: C5543446; OMIM: 619340

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001653308	OMIM	no assertion criteria provided	Pathogenic (May 28, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004102717	Daryl Scott Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 10, 2023)	de novo	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

SCV001653308

OMIM

no assertion criteria provided

Pathogenic
(May 28, 2021)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004102717

Daryl Scott Lab, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 10, 2023)

de novo

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

De novo NSF mutations cause early infantile epileptic encephalopathy.

Suzuki H, Yoshida T, Morisada N, Uehara T, Kosaki K, Sato K, Matsubara K, Takano-Shimizu T, Takenouchi T.

Ann Clin Transl Neurol. 2019 Nov;6(11):2334-2339. doi: 10.1002/acn3.50917. Epub 2019 Nov 1.

PubMed [citation]

PMID:: 31675180
PMCID:: PMC6856629

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 OMIM, SCV001653308.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 3-year-old girl, born of unrelated Japanese parents, with developmental and epileptic encephalopathy-96 (DEE96; 619340), Suzuki et al. (2019) identified a de novo heterozygous c.1688C-T transition (c.1688C-T, NM_006178.3) in the NSF gene, resulting in a pro563-to-leu (P563L) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was absent from the ExAC database and from a cohort of 2,049 Japanese control individuals. Studies of patient cells were not performed. Transfection of the mutation into the Drosophila eye disc resulted in defective eye development with increased cellular apoptosis, suggesting that the gene is involved in neuronal development. Pan-neuronal expression of the mutation in Drosophila was embryonic lethal.

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

From Daryl Scott Lab, Baylor College of Medicine, SCV004102717.1

#	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	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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