rs199469635
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Very_Strong
The NM_017415.3(KLHL3):c.1582C>T(p.Arg528Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 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 Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R528H) has been classified as Pathogenic.
Frequency
Consequence
NM_017415.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLHL3 | NM_017415.3 | c.1582C>T | p.Arg528Cys | missense_variant | 13/15 | ENST00000309755.9 | |
KLHL3 | NM_001257194.1 | c.1486C>T | p.Arg496Cys | missense_variant | 13/15 | ||
KLHL3 | NM_001257195.2 | c.1336C>T | p.Arg446Cys | missense_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLHL3 | ENST00000309755.9 | c.1582C>T | p.Arg528Cys | missense_variant | 13/15 | 1 | NM_017415.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727224
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Pseudohypoaldosteronism type 2D Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 02, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 11, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 11, 2012 | - - |
Pseudohypoaldosteronism type 2A Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Richard Lifton Laboratory, Yale University School of Medicine | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at