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GeneBe

rs5219

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_000525.4(KCNJ11):c.67A>T(p.Lys23Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 35)

Consequence

KCNJ11
NM_000525.4 stop_gained

Scores

1
3
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.12
Variant links:
Genes affected
KCNJ11 (HGNC:6257): (potassium inwardly rectifying channel subfamily J member 11) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. There are 122 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCNJ11NM_000525.4 linkuse as main transcriptc.67A>T p.Lys23Ter stop_gained 1/1 ENST00000339994.5
KCNJ11NM_001377296.1 linkuse as main transcriptc.-24A>T 5_prime_UTR_variant 2/3
KCNJ11NM_001166290.2 linkuse as main transcriptc.-16-179A>T intron_variant
KCNJ11NM_001377297.1 linkuse as main transcriptc.-16-179A>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCNJ11ENST00000339994.5 linkuse as main transcriptc.67A>T p.Lys23Ter stop_gained 1/1 NM_000525.4 P1Q14654-1

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
Cov.:
64
GnomAD4 genome
Cov.:
35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.59
D
BayesDel_noAF
Uncertain
0.070
Cadd
Pathogenic
38
Dann
Uncertain
0.99
Eigen
Uncertain
0.20
Eigen_PC
Benign
-0.057
FATHMM_MKL
Benign
0.50
N
MutationTaster
Benign
1.0
D;D
Vest4
0.39
GERP RS
4.3

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5219; hg19: chr11-17409572; API