1-34784760-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting
The NM_024009.3(GJB3):c.-3G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024009.3 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJB3 | NM_024009.3 | c.-3G>A | 5_prime_UTR_variant | Exon 2 of 2 | ENST00000373366.3 | NP_076872.1 | ||
GJB3 | NM_001005752.2 | c.-3G>A | 5_prime_UTR_variant | Exon 2 of 2 | NP_001005752.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GJB3 | ENST00000373366 | c.-3G>A | 5_prime_UTR_variant | Exon 2 of 2 | 1 | NM_024009.3 | ENSP00000362464.2 | |||
GJB3 | ENST00000373362 | c.-3G>A | 5_prime_UTR_variant | Exon 2 of 2 | 1 | ENSP00000362460.3 | ||||
SMIM12 | ENST00000426886.1 | n.208-66351C>T | intron_variant | Intron 2 of 4 | 1 | ENSP00000429902.1 | ||||
ENSG00000255811 | ENST00000542839.1 | n.110+3228C>T | intron_variant | Intron 1 of 1 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250736Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135542
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461424Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727000
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74436
ClinVar
Submissions by phenotype
not provided Uncertain:1
Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Has not been previously published as pathogenic or benign to our knowledge -
Erythrokeratodermia variabilis et progressiva 1 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at