15-85768168-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_022480.4(KLHL25):c.1643G>T(p.Gly548Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_022480.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLHL25 | NM_022480.4 | c.1643G>T | p.Gly548Val | missense_variant | Exon 2 of 3 | ENST00000337975.6 | NP_071925.2 | |
KLHL25 | XM_047432937.1 | c.1643G>T | p.Gly548Val | missense_variant | Exon 2 of 3 | XP_047288893.1 | ||
KLHL25 | XM_047432938.1 | c.1643G>T | p.Gly548Val | missense_variant | Exon 2 of 3 | XP_047288894.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727244
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1643G>T (p.G548V) alteration is located in exon 2 (coding exon 1) of the KLHL25 gene. This alteration results from a G to T substitution at nucleotide position 1643, causing the glycine (G) at amino acid position 548 to be replaced by a valine (V). 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