chr11-17387075-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000525.4(KCNJ11):c.1017G>A(p.Val339Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
KCNJ11
NM_000525.4 synonymous
NM_000525.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.614
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 Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 11-17387075-C-T is Benign according to our data. Variant chr11-17387075-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1607360.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| KCNJ11 | NM_000525.4 | c.1017G>A | p.Val339Val | synonymous_variant | 1/1 | ENST00000339994.5 | NP_000516.3 | |
| KCNJ11 | NM_001166290.2 | c.756G>A | p.Val252Val | synonymous_variant | 2/2 | NP_001159762.1 | ||
| KCNJ11 | NM_001377296.1 | c.756G>A | p.Val252Val | synonymous_variant | 3/3 | NP_001364225.1 | ||
| KCNJ11 | NM_001377297.1 | c.756G>A | p.Val252Val | synonymous_variant | 2/2 | NP_001364226.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| KCNJ11 | ENST00000339994.5 | c.1017G>A | p.Val339Val | synonymous_variant | 1/1 | 6 | NM_000525.4 | ENSP00000345708.4 | ||
| KCNJ11 | ENST00000528731.1 | c.756G>A | p.Val252Val | synonymous_variant | 2/2 | 1 | ENSP00000434755.1 | |||
| KCNJ11 | ENST00000682350.1 | c.756G>A | p.Val252Val | synonymous_variant | 2/2 | ENSP00000508090.1 | ||||
| KCNJ11 | ENST00000682764.1 | c.756G>A | p.Val252Val | synonymous_variant | 2/3 | ENSP00000506780.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251476Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727240
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GnomAD4 genome 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74364
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
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 with Neonatal Diabetes. However, no sufficient evidence is found to ascertain the role of rs770408379 variant in MODY yet. - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 15, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at