rs2946642
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001101362.3(KBTBD13):c.378G>T(p.Ala126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,481,882 control chromosomes in the GnomAD database, including 123,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.45 ( 16011 hom., cov: 34)
Exomes 𝑓: 0.40 ( 107422 hom. )
Consequence
KBTBD13
NM_001101362.3 synonymous
NM_001101362.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.272
Genes affected
KBTBD13 (HGNC:37227): (kelch repeat and BTB domain containing 13) The gene belongs to a family of genes encoding proteins containing a BTB domain and several kelch repeats. The BTB domain functions as a protein-protein interaction module, which includes an ability to self-associate or to interact with non-BTB domain-containing proteins. The kelch motif typically occurs in groups of five to seven repeats, and has been found in proteins with diverse functions. Known functions of these family members include transcription regulation, ion channel tetramerization and gating, protein ubiquitination or degradation, and cytoskeleton regulation. The exact function of this family member has yet to be determined. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 15-65077193-G-T is Benign according to our data. Variant chr15-65077193-G-T is described in ClinVar as [Benign]. Clinvar id is 129309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-65077193-G-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.272 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KBTBD13 | NM_001101362.3 | c.378G>T | p.Ala126= | synonymous_variant | 1/1 | ENST00000432196.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KBTBD13 | ENST00000432196.5 | c.378G>T | p.Ala126= | synonymous_variant | 1/1 | NM_001101362.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.449 AC: 68187AN: 151734Hom.: 15983 Cov.: 34
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GnomAD3 exomes AF: 0.467 AC: 44457AN: 95214Hom.: 10771 AF XY: 0.449 AC XY: 23988AN XY: 53418
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GnomAD4 exome AF: 0.397 AC: 527645AN: 1330040Hom.: 107422 Cov.: 52 AF XY: 0.395 AC XY: 257983AN XY: 653144
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GnomAD4 genome ? AF: 0.450 AC: 68258AN: 151842Hom.: 16011 Cov.: 34 AF XY: 0.451 AC XY: 33453AN XY: 74222
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 17, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 22, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Nemaline myopathy 6 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at