NM_133261.3(GIPC3):c.122C>A (p.Thr41Lys) AND Rare genetic deafness

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 18, 2016
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:: RCV000150720.6

Allele description [Variation Report for NM_133261.3(GIPC3):c.122C>A (p.Thr41Lys)]

NM_133261.3(GIPC3):c.122C>A (p.Thr41Lys)

Gene:

GIPC3:GIPC PDZ domain containing family member 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_133261.3(GIPC3):c.122C>A (p.Thr41Lys)

HGVS:

NC_000019.10:g.3585719C>A
NG_031943.1:g.5149C>A
NM_133261.3:c.122C>AMANE SELECT
NP_573568.1:p.Thr41Lys
NC_000019.9:g.3585717C>A
NM_133261.2:c.122C>A

Protein change:

T41K

Links:

dbSNP: rs727503062

NCBI 1000 Genomes Browser:

rs727503062

Molecular consequence:

NM_133261.3:c.122C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000198138	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (May 18, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23510777, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000198138

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(May 18, 2016)

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	4	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Homozygosity mapping identifies a novel GIPC3 mutation causing congenital nonsyndromic hearing loss in a Saudi family.

Ramzan K, Al-Owain M, Allam R, Berhan A, Abuharb G, Taibah K, Imtiaz F.

Gene. 2013 May 25;521(1):195-9. doi: 10.1016/j.gene.2013.03.042. Epub 2013 Mar 16.

PubMed [citation]

PMID:: 23510777

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, SCV000198138.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (2)

Description

The p.Thr41Lys variant in GIPC3 has been previously identified in one consanguin eous Saudi Arabian family with prelingual severe to profound sensorineural heari ng loss and was not identified among 400 ethnically matched control chromosomes (Ramzan 2013). The Thr41Lys variant segregated in the homozygous state in five a ffected siblings, while the parents and two unaffected siblings were either hete rozygous for the variant or were wild-type (Ramzan 2013). However, the reported segregation data cannot rule out linkage disequilibrium between the Thr41Lys var iant and another causative variant. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pa thogenic based on the segregation data from the previously reported family.

#	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	1	not provided

Last Updated: Apr 7, 2025

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