rs145438428
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_001110219.3(GJB6):c.405G>A(p.Thr135Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,613,688 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_001110219.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJB6 | NM_001110219.3 | c.405G>A | p.Thr135Thr | synonymous_variant | Exon 5 of 5 | ENST00000647029.1 | NP_001103689.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000513 AC: 78AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000215 AC: 54AN: 251416Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135880
GnomAD4 exome AF: 0.000205 AC: 300AN: 1461474Hom.: 0 Cov.: 32 AF XY: 0.000198 AC XY: 144AN XY: 727070
GnomAD4 genome AF: 0.000512 AC: 78AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74432
ClinVar
Submissions by phenotype
Hidrotic ectodermal dysplasia syndrome Uncertain: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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:1
p.Thr135Thr in exon 03 of GJB6: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.2% (38/24034) of A frican chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs145438428). -
Hidrotic ectodermal dysplasia syndrome;C2673759:Autosomal recessive nonsyndromic hearing loss 1A;C2675235:Autosomal recessive nonsyndromic hearing loss 1B;C2675237:Autosomal dominant nonsyndromic hearing loss 3B Benign:1
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GJB6-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