15-65076838-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001101362.3(KBTBD13):c.23T>C(p.Leu8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,552,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L8L) has been classified as Likely benign.
Frequency
Consequence
NM_001101362.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KBTBD13 | NM_001101362.3 | c.23T>C | p.Leu8Pro | missense_variant | 1/1 | ENST00000432196.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KBTBD13 | ENST00000432196.5 | c.23T>C | p.Leu8Pro | missense_variant | 1/1 | NM_001101362.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000179 AC: 3AN: 167238Hom.: 0 AF XY: 0.0000218 AC XY: 2AN XY: 91694
GnomAD4 exome AF: 0.0000179 AC: 25AN: 1400538Hom.: 0 Cov.: 29 AF XY: 0.0000144 AC XY: 10AN XY: 692110
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74506
ClinVar
Submissions by phenotype
Nemaline myopathy 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 23, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with KBTBD13-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 8 of the KBTBD13 protein (p.Leu8Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at