rs80356618
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_000525.4(KCNJ11):c.497G>T(p.Cys166Phe) 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. Variant has been reported in ClinVar as drug response (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C166W) has been classified as Pathogenic.
Frequency
Consequence
NM_000525.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNJ11 | NM_000525.4 | c.497G>T | p.Cys166Phe | missense_variant | 1/1 | ENST00000339994.5 | NP_000516.3 | |
KCNJ11 | NM_001166290.2 | c.236G>T | p.Cys79Phe | missense_variant | 2/2 | NP_001159762.1 | ||
KCNJ11 | NM_001377296.1 | c.236G>T | p.Cys79Phe | missense_variant | 3/3 | NP_001364225.1 | ||
KCNJ11 | NM_001377297.1 | c.236G>T | p.Cys79Phe | missense_variant | 2/2 | NP_001364226.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNJ11 | ENST00000339994.5 | c.497G>T | p.Cys166Phe | missense_variant | 1/1 | NM_000525.4 | ENSP00000345708 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 63
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Diabetes mellitus, permanent neonatal 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2006 | - - |
Glibenclamide response Other:1
drug response, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which may be responsive to oral sulfonylureas. However, this particular variant rs80356618 is associated with poor response to glibenclamide. - |
Permanent neonatal diabetes mellitus Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at