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NM_004568.6(SERPINB6):c.733G>T (p.Glu245Ter) AND Autosomal recessive nonsyndromic hearing loss 91

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 14, 2010
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000014571.26

Allele description [Variation Report for NM_004568.6(SERPINB6):c.733G>T (p.Glu245Ter)]

NM_004568.6(SERPINB6):c.733G>T (p.Glu245Ter)

Gene:
SERPINB6:serpin family B member 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p25.2
Genomic location:
Preferred name:
NM_004568.6(SERPINB6):c.733G>T (p.Glu245Ter)
HGVS:
  • NC_000006.12:g.2948696C>A
  • NG_027692.1:g.28470G>T
  • NM_001195291.3:c.745G>T
  • NM_001271822.2:c.775G>T
  • NM_001271823.2:c.790G>T
  • NM_001271824.2:c.733G>T
  • NM_001271825.2:c.733G>T
  • NM_001297699.2:c.733G>T
  • NM_001297700.2:c.733G>T
  • NM_001374515.1:c.745G>T
  • NM_001374516.1:c.733G>T
  • NM_001374517.1:c.601G>T
  • NM_004568.6:c.733G>TMANE SELECT
  • NP_001182220.2:p.Glu249Ter
  • NP_001258751.1:p.Glu259Ter
  • NP_001258752.1:p.Glu264Ter
  • NP_001258753.1:p.Glu245Ter
  • NP_001258754.1:p.Glu245Ter
  • NP_001284628.1:p.Glu245Ter
  • NP_001284629.1:p.Glu245Ter
  • NP_001361444.1:p.Glu249Ter
  • NP_001361445.1:p.Glu245Ter
  • NP_001361446.1:p.Glu201Ter
  • NP_004559.4:p.Glu245Ter
  • NC_000006.11:g.2948930C>A
  • NR_164657.1:n.782G>T
Protein change:
E201*; GLU245TER
Links:
OMIM: 173321.0001; dbSNP: rs267607037
NCBI 1000 Genomes Browser:
rs267607037
Molecular consequence:
  • NR_164657.1:n.782G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001195291.3:c.745G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001271822.2:c.775G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001271823.2:c.790G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001271824.2:c.733G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001271825.2:c.733G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001297699.2:c.733G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001297700.2:c.733G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374515.1:c.745G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374516.1:c.733G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374517.1:c.601G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004568.6:c.733G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Autosomal recessive nonsyndromic hearing loss 91
Synonyms:
Deafness, autosomal recessive 91
Identifiers:
MONDO: MONDO:0013269; MedGen: C3150704; Orphanet: 90636; OMIM: 613453

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000034825OMIM
no assertion criteria provided
Pathogenic
(May 14, 2010) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A truncating mutation in SERPINB6 is associated with autosomal-recessive nonsyndromic sensorineural hearing loss.

Sirmaci A, Erbek S, Price J, Huang M, Duman D, Cengiz FB, Bademci G, Tokgöz-Yilmaz S, Hişmi B, Ozdağ H, Oztürk B, Kulaksizoğlu S, Yildirim E, Kokotas H, Grigoriadou M, Petersen MB, Shahin H, Kanaan M, King MC, Chen ZY, Blanton SH, Liu XZ, et al.

Am J Hum Genet. 2010 May 14;86(5):797-804. doi: 10.1016/j.ajhg.2010.04.004. Epub 2010 May 6.

PubMed [citation]
PMID:
20451170
PMCID:
PMC2869020

Details of each submission

From OMIM, SCV000034825.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In affected members of a consanguineous Turkish family with nonsyndromic progressive hearing loss (DFNB91; 613453), Sirmaci et al. (2010) identified a homozygous 744G-T transversion in the SERPINB6 gene, resulting in a gly245-to-ter (E245X) substitution, which removes 131 amino acids in the C-terminal region that includes the reactive center loop. Further studies showed that the mutation resulted in mRNA decay and complete lack of protein expression. The mutation was not found in 300 Turkish controls or in an additional 542 Turkish, Greek, American, and Palestinian families, mostly with congenital hearing loss. In vitro functional expression studies in HeLa cells showed that the E245X mutation resulted in increased loss of lysosomal integrity in response to osmotic shock compared to cells transfected with wildtype SERPINB6. These findings suggested that wildtype SERPINB6 is required to counter potentially cytotoxic components of leaking lysosomal proteases that result from various stress conditions. Although the precise age of onset could not be ascertained, the youngest affected individual, who was 23 years old, reported loss of hearing after age 20. The hearing loss was progressive and age-dependent, consistent with a loss of function of an intracellular protease inhibitor.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 23, 2022