rs5215
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000525.4(KCNJ11):c.1009G>A(p.Val337Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,613,990 control chromosomes in the GnomAD database, including 342,278 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000525.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ11 | NM_000525.4 | c.1009G>A | p.Val337Ile | missense_variant | 1/1 | ENST00000339994.5 | |
KCNJ11 | NM_001166290.2 | c.748G>A | p.Val250Ile | missense_variant | 2/2 | ||
KCNJ11 | NM_001377296.1 | c.748G>A | p.Val250Ile | missense_variant | 3/3 | ||
KCNJ11 | NM_001377297.1 | c.748G>A | p.Val250Ile | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ11 | ENST00000339994.5 | c.1009G>A | p.Val337Ile | missense_variant | 1/1 | NM_000525.4 | P1 | ||
KCNJ11 | ENST00000528731.1 | c.748G>A | p.Val250Ile | missense_variant | 2/2 | 1 | |||
KCNJ11 | ENST00000682350.1 | c.748G>A | p.Val250Ile | missense_variant | 2/2 | ||||
KCNJ11 | ENST00000682764.1 | c.748G>A | p.Val250Ile | missense_variant | 2/3 |
Frequencies
GnomAD3 genomes ? AF: 0.708 AC: 107545AN: 152006Hom.: 39303 Cov.: 34
GnomAD3 exomes AF: 0.638 AC: 160506AN: 251456Hom.: 52127 AF XY: 0.634 AC XY: 86160AN XY: 135914
GnomAD4 exome AF: 0.641 AC: 937700AN: 1461864Hom.: 302925 Cov.: 73 AF XY: 0.639 AC XY: 464957AN XY: 727236
GnomAD4 genome ? AF: 0.708 AC: 107657AN: 152126Hom.: 39353 Cov.: 34 AF XY: 0.702 AC XY: 52184AN XY: 74352
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 02, 2021 | - - |
Diabetes mellitus, transient neonatal, 3 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jul 01, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 10, 2018 | This variant is associated with the following publications: (PMID: 31118516, 30389748, 26551672, 27398621, 17257281, 22958899) - |
Hyperinsulinemic hypoglycemia, familial, 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jul 01, 2021 | - - |
Diabetes mellitus, permanent neonatal 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jul 01, 2021 | - - |
Permanent neonatal diabetes mellitus Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Maturity-onset diabetes of the young type 13 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Type 2 diabetes mellitus Other:1
association, no assertion criteria provided | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Mutations can cause decreased production of insulin and secretion. This can lead to MODY which is responsive to oral sulfonylureas. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at