rs200548009
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001101362.3(KBTBD13):c.98G>A(p.Arg33Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000257 in 1,562,446 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R33G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001101362.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000192 AC: 33AN: 171546Hom.: 0 AF XY: 0.000170 AC XY: 16AN XY: 94218
GnomAD4 exome AF: 0.000274 AC: 386AN: 1410106Hom.: 0 Cov.: 29 AF XY: 0.000269 AC XY: 188AN XY: 698636
GnomAD4 genome AF: 0.000105 AC: 16AN: 152340Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74494
ClinVar
Submissions by phenotype
KBTBD13-related disorder Uncertain:1
The KBTBD13 c.98G>A variant is predicted to result in the amino acid substitution p.Arg33Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.037% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Inborn genetic diseases Uncertain:1
The c.98G>A (p.R33Q) alteration is located in exon 1 (coding exon 1) of the KBTBD13 gene. This alteration results from a G to A substitution at nucleotide position 98, causing the arginine (R) at amino acid position 33 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Nemaline myopathy 6 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 33 of the KBTBD13 protein (p.Arg33Gln). This variant is present in population databases (rs200548009, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with KBTBD13-related conditions. ClinVar contains an entry for this variant (Variation ID: 464365). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt KBTBD13 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at