15-85768046-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022480.4(KLHL25):c.1765G>A(p.Ala589Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000746 in 1,609,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. A589V) has been classified as Uncertain significance.
Frequency
Consequence
NM_022480.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLHL25 | NM_022480.4 | c.1765G>A | p.Ala589Thr | missense_variant | Exon 2 of 3 | ENST00000337975.6 | NP_071925.2 | |
KLHL25 | XM_047432937.1 | c.1765G>A | p.Ala589Thr | missense_variant | Exon 2 of 3 | XP_047288893.1 | ||
KLHL25 | XM_047432938.1 | c.1765G>A | p.Ala589Thr | missense_variant | Exon 2 of 3 | XP_047288894.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152158Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000885 AC: 22AN: 248482Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134302
GnomAD4 exome AF: 0.0000734 AC: 107AN: 1456874Hom.: 0 Cov.: 31 AF XY: 0.0000815 AC XY: 59AN XY: 723784
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74328
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1765G>A (p.A589T) alteration is located in exon 2 (coding exon 1) of the KLHL25 gene. This alteration results from a G to A substitution at nucleotide position 1765, causing the alanine (A) at amino acid position 589 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at