rs587777437
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000890.5(KCNJ5):c.452G>A(p.Gly151Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G151R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000890.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ5 | NM_000890.5 | c.452G>A | p.Gly151Glu | missense_variant | 2/3 | ENST00000529694.6 | |
KCNJ5 | NM_001354169.2 | c.452G>A | p.Gly151Glu | missense_variant | 3/4 | ||
KCNJ5 | XM_011542810.4 | c.452G>A | p.Gly151Glu | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ5 | ENST00000529694.6 | c.452G>A | p.Gly151Glu | missense_variant | 2/3 | 1 | NM_000890.5 | P1 | |
KCNJ5 | ENST00000338350.4 | c.452G>A | p.Gly151Glu | missense_variant | 3/4 | 1 | P1 | ||
KCNJ5 | ENST00000533599.1 | c.452G>A | p.Gly151Glu | missense_variant | 1/2 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 58
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial hyperaldosteronism type III Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 14, 2012 | - - |
Long QT syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2019 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly151 amino acid residue in KCNJ5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22308486, 24819081). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been reported to affect KCNJ5 protein function (PMID: 22203740, 22308486). This variant has been observed to segregate with hyperaldosteronism in families (PMID: 22203740, 22308486). ClinVar contains an entry for this variant (Variation ID: 135679). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 151 of the KCNJ5 protein (p.Gly151Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at