rs1303411209
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5BS2
The NM_001101362.3(KBTBD13):c.244G>A(p.Val82Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000441 in 1,359,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V82V) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000044 ( 0 hom. )
Consequence
KBTBD13
NM_001101362.3 missense
NM_001101362.3 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 4.95
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 Likely_benign. Variant got -3 ACMG points.
PP5
?
Variant 15-65077059-G-A is Pathogenic according to our data. Variant chr15-65077059-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435545.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=2, Pathogenic=1}.
BS2
?
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KBTBD13 | NM_001101362.3 | c.244G>A | p.Val82Met | missense_variant | 1/1 | ENST00000432196.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KBTBD13 | ENST00000432196.5 | c.244G>A | p.Val82Met | missense_variant | 1/1 | NM_001101362.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome AF: 0.00000441 AC: 6AN: 1359662Hom.: 0 Cov.: 58 AF XY: 0.00000298 AC XY: 2AN XY: 670754
GnomAD4 exome
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AC:
6
AN:
1359662
Hom.:
Cov.:
58
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AC XY:
2
AN XY:
670754
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Nemaline myopathy 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | NeuroMeGen, Hospital Clinico Santiago de Compostela | Oct 08, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 13, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at V82 (P = 0.0165);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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