NM_006393.3(NEBL):c.109T>C (p.Leu37=) AND not specified

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: May 24, 2022
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:: RCV000038678.7

Allele description [Variation Report for NM_006393.3(NEBL):c.109T>C (p.Leu37=)]

NM_006393.3(NEBL):c.109T>C (p.Leu37=)

Gene:

NEBL:nebulette [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p12.31

Genomic location:

Preferred name:

NM_006393.3(NEBL):c.109T>C (p.Leu37=)

Other names:

p.L37L:TTA>CTA

HGVS:

NC_000010.11:g.20897002A>G
NG_017092.1:g.282186T>C
NM_001173484.2:c.357+64670T>C
NM_001377322.1:c.357+64670T>C
NM_001377323.1:c.309+64670T>C
NM_001377324.1:c.300+64670T>C
NM_001377325.1:c.291+64670T>C
NM_001377326.1:c.249+64670T>C
NM_001377327.1:c.249+64670T>C
NM_001377328.1:c.249+64670T>C
NM_006393.3:c.109T>CMANE SELECT
NM_213569.2:c.357+64670T>C
NP_006384.1:p.Leu37=
NP_006384.1:p.Leu37=
LRG_411t1:c.357+64670T>C
LRG_411t2:c.109T>C
LRG_411:g.282186T>C
LRG_411p2:p.Leu37=
NC_000010.10:g.21185931A>G
NM_001173484.1:c.357+64670T>C
NM_006393.2:c.109T>C
c.109T>C
p.Leu37Leu

Links:

dbSNP: rs140734883

NCBI 1000 Genomes Browser:

rs140734883

Molecular consequence:

NM_001173484.2:c.357+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377322.1:c.357+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377323.1:c.309+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377324.1:c.300+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377325.1:c.291+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377326.1:c.249+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377327.1:c.249+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377328.1:c.249+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_213569.2:c.357+64670T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_006393.3:c.109T>C - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000062356	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (Jun 10, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000236075	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Sep 19, 2014)	germline	clinical testing	Citation Link,
SCV002734634	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (May 24, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000062356

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Benign
(Jun 10, 2015)

germline

clinical testing

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

SCV000236075

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Benign
(Sep 19, 2014)

germline

clinical testing

Citation Link,

SCV002734634

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(May 24, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	4	4	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	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, SCV000062356.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (1)

Description

p.Leu37Leu in exon 2 of NEBL: This variant is not expected to have clinical sign ificance because it has been identified in 1.3% (88/6594) of Finnish chromosomes , including 1 homozygote by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs140734883).

#	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		4	not provided	4	not provided

From GeneDx, SCV000236075.10

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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 Ambry Genetics, SCV002734634.2

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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