NM_024009.3:c.-4C>T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_024009.3(GJB3):c.-4C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,611,622 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 Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJB3 | NM_024009.3 | c.-4C>T | 5_prime_UTR_variant | Exon 2 of 2 | ENST00000373366.3 | NP_076872.1 | ||
GJB3 | NM_001005752.2 | c.-4C>T | 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.-4C>T | 5_prime_UTR_variant | Exon 2 of 2 | 1 | NM_024009.3 | ENSP00000362464.2 | |||
GJB3 | ENST00000373362 | c.-4C>T | 5_prime_UTR_variant | Exon 2 of 2 | 1 | ENSP00000362460.3 | ||||
SMIM12 | ENST00000426886.1 | n.208-66350G>A | intron_variant | Intron 2 of 4 | 1 | ENSP00000429902.1 | ||||
ENSG00000255811 | ENST00000542839.1 | n.110+3229G>A | intron_variant | Intron 1 of 1 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000997 AC: 25AN: 250628Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135514
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1459330Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 726042
GnomAD4 genome AF: 0.000341 AC: 52AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74452
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant classified as Uncertain Significance - Favor Benign. The -4C>T variant i n GJB3 has not been reported in individuals with hearing loss, but has been iden tified in 0.16% (7/4406) of African American chromosomes by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs200902087). This vari ant occurs 4 bp upstream of the translation initiation site in the 5' untranslat ed region, and, without functional studies, its impact on the translation of the protein cannot be predicted. In summary, additional data is needed to determine the clinical significance of this variant. -
GJB3-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at