chr1-34785182-CATT-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_024009.3(GJB3):c.421_423delATT(p.Ile141del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
GJB3
NM_024009.3 conservative_inframe_deletion
NM_024009.3 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.97
Publications
5 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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_024009.3. Strenght limited to Supporting due to length of the change: 1aa.
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GJB3 | NM_024009.3 | MANE Select | c.421_423delATT | p.Ile141del | conservative_inframe_deletion | Exon 2 of 2 | NP_076872.1 | ||
| GJB3 | NM_001005752.2 | c.421_423delATT | p.Ile141del | conservative_inframe_deletion | Exon 2 of 2 | NP_001005752.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GJB3 | ENST00000373366.3 | TSL:1 MANE Select | c.421_423delATT | p.Ile141del | conservative_inframe_deletion | Exon 2 of 2 | ENSP00000362464.2 | ||
| GJB3 | ENST00000373362.3 | TSL:1 | c.421_423delATT | p.Ile141del | conservative_inframe_deletion | Exon 2 of 2 | ENSP00000362460.3 | ||
| SMIM12 | ENST00000426886.1 | TSL:1 | n.208-66776_208-66774delAAT | intron | N/A | ENSP00000429902.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 250942 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250942
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
AF:
Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461882Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727240 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461882
Hom.:
AF XY:
AC XY:
2
AN XY:
727240
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
2
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1112012
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hearing loss, autosomal recessive Uncertain:1
Jan 01, 2000
OMIM
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:literature only
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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