NM_006393.3(NEBL):c.561G>C (p.Gln187His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 12, 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:: RCV000151545.13

Allele description [Variation Report for NM_006393.3(NEBL):c.561G>C (p.Gln187His)]

NM_006393.3(NEBL):c.561G>C (p.Gln187His)

Gene:

NEBL:nebulette [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p12.31

Genomic location:

Preferred name:

NM_006393.3(NEBL):c.561G>C (p.Gln187His)

HGVS:

NC_000010.11:g.20869761C>G
NG_017092.1:g.309427G>C
NM_001173484.2:c.358-56821G>C
NM_001377322.1:c.358-56821G>C
NM_001377323.1:c.310-56821G>C
NM_001377324.1:c.301-56821G>C
NM_001377325.1:c.292-56821G>C
NM_001377326.1:c.250-56821G>C
NM_001377327.1:c.250-56821G>C
NM_001377328.1:c.250-56821G>C
NM_006393.3:c.561G>CMANE SELECT
NM_213569.2:c.358-56821G>C
NP_006384.1:p.Gln187His
NP_006384.1:p.Gln187His
LRG_411t1:c.358-56821G>C
LRG_411t2:c.561G>C
LRG_411:g.309427G>C
LRG_411p2:p.Gln187His
NC_000010.10:g.21158690C>G
NM_006393.2:c.561G>C
O76041:p.Gln187His

Protein change:

Q187H

Links:

UniProtKB: O76041#VAR_010289; dbSNP: rs75301590

NCBI 1000 Genomes Browser:

rs75301590

Molecular consequence:

NM_001173484.2:c.358-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377322.1:c.358-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377323.1:c.310-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377324.1:c.301-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377325.1:c.292-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377326.1:c.250-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377327.1:c.250-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001377328.1:c.250-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_213569.2:c.358-56821G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_006393.3:c.561G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000199674	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Mar 12, 2015)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11140941, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000199674

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Mar 12, 2015)

germline

clinical testing

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

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

Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy.

Arimura T, Nakamura T, Hiroi S, Satoh M, Takahashi M, Ohbuchi N, Ueda K, Nouchi T, Yamaguchi N, Akai J, Matsumori A, Sasayama S, Kimura A.

Hum Genet. 2000 Nov;107(5):440-51.

PubMed [citation]

PMID:: 11140941

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, SCV000199674.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Gln187His var iant in NEBL has been identified in 1 Japanese individual with DCM (Arimura 2000 ) and 1 Asian adult with HCM, who carried a pathogenic variant in a different HC M gene (LMM unpublished data). This variant has also been identified in 0.2% (17 /8642) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs75301590). Glutamine (Gln) at position 187 i s not conserved in mammals and 1 mammal (aardvark) has a histidine (His) at this position, raising the possibility that this change may be tolerated. Additional computational prediction tools do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Gln1 87His variant is uncertain, its frequency suggests that it is more likely to be benign.

#	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: Apr 15, 2024

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