rs558291810
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_001101362.3(KBTBD13):c.815T>A(p.Ile272Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,590,312 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00052 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000045 ( 1 hom. )
Consequence
KBTBD13
NM_001101362.3 missense
NM_001101362.3 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 7.80
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 -11 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.081732064).
BP6
Variant 15-65077630-T-A is Benign according to our data. Variant chr15-65077630-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 464362.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000519 (79/152114) while in subpopulation AFR AF= 0.0019 (79/41520). AF 95% confidence interval is 0.00156. There are 0 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High AC in GnomAd4 at 79 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KBTBD13 | NM_001101362.3 | c.815T>A | p.Ile272Asn | missense_variant | 1/1 | ENST00000432196.5 | NP_001094832.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KBTBD13 | ENST00000432196.5 | c.815T>A | p.Ile272Asn | missense_variant | 1/1 | NM_001101362.3 | ENSP00000388723 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000513 AC: 78AN: 151996Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000117 AC: 24AN: 205834Hom.: 0 AF XY: 0.0000608 AC XY: 7AN XY: 115106
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GnomAD4 exome AF: 0.0000452 AC: 65AN: 1438198Hom.: 1 Cov.: 83 AF XY: 0.0000350 AC XY: 25AN XY: 715118
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GnomAD4 genome AF: 0.000519 AC: 79AN: 152114Hom.: 0 Cov.: 34 AF XY: 0.000484 AC XY: 36AN XY: 74384
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.815T>A (p.I272N) alteration is located in exon 1 (coding exon 1) of the KBTBD13 gene. This alteration results from a T to A substitution at nucleotide position 815, causing the isoleucine (I) at amino acid position 272 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
KBTBD13-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 19, 2023 | 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). - |
Nemaline myopathy 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 21, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of disorder (P = 0.0326);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
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