rs17642086
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_002239.4(KCNJ3):āc.1038T>Cā(p.His346=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,613,570 control chromosomes in the GnomAD database, including 82,959 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.27 ( 6312 hom., cov: 31)
Exomes š: 0.31 ( 76647 hom. )
Consequence
KCNJ3
NM_002239.4 synonymous
NM_002239.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.201
Genes affected
KCNJ3 (HGNC:6264): (potassium inwardly rectifying channel subfamily J member 3) 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 plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex that also couples to neurotransmitter receptors in the brain and whereby channel activation can inhibit action potential firing by hyperpolarizing the plasma membrane. These multimeric G-protein-gated inwardly-rectifying potassium (GIRK) channels may play a role in the pathophysiology of epilepsy, addiction, Down's syndrome, ataxia, and Parkinson's disease. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP7
?
Synonymous conserved (PhyloP=0.201 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNJ3 | NM_002239.4 | c.1038T>C | p.His346= | synonymous_variant | 3/3 | ENST00000295101.3 | |
KCNJ3 | NM_001260508.2 | c.*113T>C | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNJ3 | ENST00000295101.3 | c.1038T>C | p.His346= | synonymous_variant | 3/3 | 1 | NM_002239.4 | P1 | |
KCNJ3 | ENST00000544049.2 | c.*113T>C | 3_prime_UTR_variant | 2/2 | 1 | ||||
KCNJ3 | ENST00000651198.1 | c.501T>C | p.His167= | synonymous_variant | 4/4 | ||||
KCNJ3 | ENST00000493505.1 | n.381T>C | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.267 AC: 40612AN: 151874Hom.: 6312 Cov.: 31
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GnomAD3 exomes AF: 0.263 AC: 66003AN: 251236Hom.: 10240 AF XY: 0.265 AC XY: 36020AN XY: 135778
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GnomAD4 exome AF: 0.314 AC: 459528AN: 1461576Hom.: 76647 Cov.: 35 AF XY: 0.311 AC XY: 225905AN XY: 727104
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GnomAD4 genome ? AF: 0.267 AC: 40626AN: 151994Hom.: 6312 Cov.: 31 AF XY: 0.265 AC XY: 19708AN XY: 74276
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at