GJB3 p.Val33Val

Variant names:

• chr1-34784858-G-G
• NM_024009.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-34784859--
• chr1-34784861-G-T
• chr1-34784861-G-C
• chr1-34784861-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024009.3(GJB3):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GJB3 NM_024009.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28
• Publications: 0 publications found

Genes affected

GJB3 (HGNC:4285): (gap junction protein beta 3) This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene can cause non-syndromic deafness or erythrokeratodermia variabilis, a skin disorder. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255811 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024009.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB3	NM_024009.3	MANE Select	c.		exon_region	Exon 2 of 2	NP_076872.1	O75712
	GJB3	NM_001005752.2		c.		exon_region	Exon 2 of 2	NP_001005752.1	O75712

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM12	ENST00000426886.1	TSL:1	n.		intron	N/A	ENSP00000429902.1	E5RH51
	ENSG00000255811	ENST00000542839.1	TSL:5	n.		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-35250459;