1-34785183-ATT-GTA

Variant names:

• chr1-34785183-ATT-GTA
• NM_024009.3:c.421_423delATTinsGTA
• GJB3 p.Ile141Val

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_024009.3(GJB3):​c.421_423delATTinsGTA​(p.Ile141Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I141T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GJB3 NM_024009.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.97
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.421_423delATTinsGTA	p.Ile141Val	missense	N/A	NP_076872.1	O75712
	GJB3	NM_001005752.2		c.421_423delATTinsGTA	p.Ile141Val	missense	N/A	NP_001005752.1	O75712

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB3	ENST00000373366.3	TSL:1 MANE Select	c.421_423delATTinsGTA	p.Ile141Val	missense	N/A	ENSP00000362464.2	O75712
	GJB3	ENST00000373362.3	TSL:1	c.421_423delATTinsGTA	p.Ile141Val	missense	N/A	ENSP00000362460.3	O75712
	SMIM12	ENST00000426886.1	TSL:1	n.208-66776_208-66774delAATinsTAC		intron	N/A	ENSP00000429902.1	E5RH51

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

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: chr1-35250784;