NM_024009.3(GJB3):c.35G>A (p.Gly12Asp) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 13, 2022
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:: RCV002512854.2

Allele description [Variation Report for NM_024009.3(GJB3):c.35G>A (p.Gly12Asp)]

NM_024009.3(GJB3):c.35G>A (p.Gly12Asp)

Gene:

GJB3:gap junction protein beta 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.3

Genomic location:

Preferred name:

NM_024009.3(GJB3):c.35G>A (p.Gly12Asp)

HGVS:

NC_000001.11:g.34784797G>A
NG_008309.1:g.8609G>A
NM_001005752.2:c.35G>A
NM_024009.3:c.35G>AMANE SELECT
NP_001005752.1:p.Gly12Asp
NP_076872.1:p.Gly12Asp
NC_000001.10:g.35250398G>A
O75712:p.Gly12Asp

Protein change:

G12D; GLY12ASP

Links:

UniProtKB: O75712#VAR_002147; OMIM: 603324.0002; dbSNP: rs74315316

NCBI 1000 Genomes Browser:

rs74315316

Molecular consequence:

NM_001005752.2:c.35G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024009.3:c.35G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003523186	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 13, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9843209, 12165562, 12702148, 19755382, 12648223, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523186

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 13, 2022)

germline

clinical testing

PubMed (6)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis.

Richard G, Smith LE, Bailey RA, Itin P, Hohl D, Epstein EH Jr, DiGiovanna JJ, Compton JG, Bale SJ.

Nat Genet. 1998 Dec;20(4):366-9.

PubMed [citation]

PMID:: 9843209

Defective trafficking and cell death is characteristic of skin disease-associated connexin 31 mutations.

Di WL, Monypenny J, Common JE, Kennedy CT, Holland KA, Leigh IM, Rugg EL, Zicha D, Kelsell DP.

Hum Mol Genet. 2002 Aug 15;11(17):2005-14.

PubMed [citation]

PMID:: 12165562

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV003523186.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly12 amino acid residue in GJB3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9843209). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects GJB3 function (PMID: 12165562, 12702148, 19755382). ClinVar contains an entry for this variant (Variation ID: 6483). This missense change has been observed in individual(s) with erythrokeratodermia variabilis (PMID: 12648223). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 12 of the GJB3 protein (p.Gly12Asp).

#	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: Feb 14, 2024

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