chr15-65076817-T-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PVS1_SupportingBP6BS2
The NM_001101362.3(KBTBD13):āc.2T>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,525,166 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_001101362.3 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000123 AC: 18AN: 145786Hom.: 0 AF XY: 0.000125 AC XY: 10AN XY: 79946
GnomAD4 exome AF: 0.000389 AC: 534AN: 1372956Hom.: 0 Cov.: 29 AF XY: 0.000375 AC XY: 253AN XY: 674558
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74366
ClinVar
Submissions by phenotype
Nemaline myopathy 6 Uncertain:2
The KBTBD13 p.Met1Arg variant is predicted to disrupt the initiation codon, and may interfere with protein expression. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of start lost variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
This sequence change affects the initiator methionine of the KBTBD13 mRNA. The next in-frame methionine is located at codon 40. This variant is present in population databases (rs374196960, gnomAD 0.03%). 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: 464353). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
not provided Benign:1
Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at