rs80356617
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 10P and 2B. PM1PM2PM5PP3_StrongBP6_Moderate
The NM_000525.4(KCNJ11):c.176T>G(p.Val59Gly) 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V59M) has been classified as Likely 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 | UniProt |
---|---|---|---|---|---|---|---|
KCNJ11 | NM_000525.4 | c.176T>G | p.Val59Gly | missense_variant | 1/1 | ENST00000339994.5 | |
KCNJ11 | NM_001166290.2 | c.-16-70T>G | intron_variant | ||||
KCNJ11 | NM_001377296.1 | c.-16-70T>G | intron_variant | ||||
KCNJ11 | NM_001377297.1 | c.-16-70T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ11 | ENST00000339994.5 | c.176T>G | p.Val59Gly | missense_variant | 1/1 | NM_000525.4 | 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 | Dec 14, 2004 | - - |
Transitory neonatal diabetes mellitus Benign:1
Likely benign, 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. This particular variant (rs80356617 -V59G) of KCNJ11 gene can result in non response to sulfonylureas in Neonatal Diabetes whereas V59A of rs80356617 of KCNJ11 gene may result in good response to oral sulfonylureas. - |
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