15-69416022-G-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001281301.2(KIF23):c.-154G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000507 in 1,578,056 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 (★).
Frequency
Consequence
NM_001281301.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIF23 | NM_001367805.3 | c.40G>T | p.Val14Leu | missense_variant | Exon 2 of 24 | ENST00000679126.1 | NP_001354734.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIF23 | ENST00000679126.1 | c.40G>T | p.Val14Leu | missense_variant | Exon 2 of 24 | NM_001367805.3 | ENSP00000504770.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000455 AC: 1AN: 219740Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 120146
GnomAD4 exome AF: 0.00000491 AC: 7AN: 1425840Hom.: 0 Cov.: 29 AF XY: 0.00000282 AC XY: 2AN XY: 708968
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74430
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 14 of the KIF23 protein (p.Val14Leu). 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 variant has not been reported in the literature in individuals affected with KIF23-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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