rs375848765
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PP3_StrongPP5
The NM_000525.4(KCNJ11):c.160C>T(p.Arg54Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000497 in 1,610,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 11/19 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54H) has been classified as Likely benign.
Frequency
Consequence
NM_000525.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ11 | NM_000525.4 | c.160C>T | p.Arg54Cys | missense_variant | 1/1 | ENST00000339994.5 | |
KCNJ11 | NM_001166290.2 | c.-16-86C>T | intron_variant | ||||
KCNJ11 | NM_001377296.1 | c.-17+86C>T | intron_variant | ||||
KCNJ11 | NM_001377297.1 | c.-16-86C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ11 | ENST00000339994.5 | c.160C>T | p.Arg54Cys | missense_variant | 1/1 | NM_000525.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251196Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135768
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1458408Hom.: 0 Cov.: 63 AF XY: 0.00000138 AC XY: 1AN XY: 724676
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Type 2 diabetes mellitus Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 04, 2023 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 22, 2017 | - - |
Maturity onset diabetes mellitus in young Uncertain:1
Uncertain significance, 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. It is also associated with Neonatal Diabetes. However, no sufficient evidence is found to ascertain the role of this particular variant (rs375848765) in MODY yet. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at