NM_006393.3(NEBL):c.109_110del (p.Leu37fs) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 18, 2015
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:: RCV000219977.4

Allele description [Variation Report for NM_006393.3(NEBL):c.109_110del (p.Leu37fs)]

NM_006393.3(NEBL):c.109_110del (p.Leu37fs)

Gene:

NEBL:nebulette [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10p12.31

Genomic location:

Preferred name:

NM_006393.3(NEBL):c.109_110del (p.Leu37fs)

HGVS:

NC_000010.11:g.20897001_20897002del
NG_017092.1:g.282186_282187del
NM_001173484.2:c.357+64670_357+64671del
NM_001377322.1:c.357+64670_357+64671del
NM_001377323.1:c.309+64670_309+64671del
NM_001377324.1:c.300+64670_300+64671del
NM_001377325.1:c.291+64670_291+64671del
NM_001377326.1:c.249+64670_249+64671del
NM_001377327.1:c.249+64670_249+64671del
NM_001377328.1:c.249+64670_249+64671del
NM_006393.3:c.109_110delMANE SELECT
NM_213569.2:c.357+64670_357+64671del
NP_006384.1:p.Leu37fs
LRG_411t1:c.357+64670_357+64671del
LRG_411:g.282186_282187del
NC_000010.10:g.21185930_21185931del
NC_000010.10:g.21185930_21185931delAA
NM_006393.2:c.109_110delTT
p.Leu37LysfsX13

Protein change:

L37fs

Links:

dbSNP: rs762005342

NCBI 1000 Genomes Browser:

rs762005342

Molecular consequence:

NM_006393.3:c.109_110del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001173484.2:c.357+64670_357+64671del - intron variant - [Sequence Ontology: SO:0001627]
NM_001377322.1:c.357+64670_357+64671del - intron variant - [Sequence Ontology: SO:0001627]
NM_001377323.1:c.309+64670_309+64671del - intron variant - [Sequence Ontology: SO:0001627]
NM_001377324.1:c.300+64670_300+64671del - intron variant - [Sequence Ontology: SO:0001627]
NM_001377325.1:c.291+64670_291+64671del - intron variant - [Sequence Ontology: SO:0001627]
NM_001377326.1:c.249+64670_249+64671del - intron variant - [Sequence Ontology: SO:0001627]
NM_001377327.1:c.249+64670_249+64671del - intron variant - [Sequence Ontology: SO:0001627]
NM_001377328.1:c.249+64670_249+64671del - intron variant - [Sequence Ontology: SO:0001627]
NM_213569.2:c.357+64670_357+64671del - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000272198	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Apr 18, 2015)	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

SCV000272198

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Apr 18, 2015)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000272198.3

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

Description

The p.Leu37Lysfs variant in NEBL has not been reported in individuals with cardi omyopathy, but has been identified in 0.2% (13/6614) of Finnish chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). This fra meshift variant is predicted to alter the protein?s amino acid sequence beginnin g at position 37 and lead to a premature termination codon 13 amino acids downst ream. This alteration is then predicted to lead to a truncated or absent protein . There is some evidence for a role of NEBL variants in dilated cardiomyopathy ( Purevjav 2010); however, the spectrum of pathogenic variants as well as the mode of inheritance is currently not well understood. In summary, despite the predi cted severe impact to the protein, the clinical significance of the p.Leu37Lysfs variant is uncertain and its frequency suggests that it is unlikely disease cau sing in the heterozygous state.

#	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		1	not provided	1	not provided

Last Updated: Dec 24, 2023

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