17-21415458-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_021012.5(KCNJ12):c.116G>A(p.Arg39Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 151,268 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 Benign (no stars).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 68)
Exomes 𝑓: 0.0076 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KCNJ12
NM_021012.5 missense
NM_021012.5 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 9.82
Genes affected
KCNJ12 (HGNC:6258): (potassium inwardly rectifying channel subfamily J member 12) This gene encodes an inwardly rectifying K+ channel which may be blocked by divalent cations. This protein is thought to be one of multiple inwardly rectifying channels which contribute to the cardiac inward rectifier current (IK1). The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]
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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 (MetaRNN=0.005340636).
BP6
Variant 17-21415458-G-A is Benign according to our data. Variant chr17-21415458-G-A is described in ClinVar as [Benign]. Clinvar id is 3059461.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNJ12 | NM_021012.5 | c.116G>A | p.Arg39Gln | missense_variant | 3/3 | ENST00000583088.6 | NP_066292.2 | |
KCNJ12 | XM_005256625.6 | c.116G>A | p.Arg39Gln | missense_variant | 3/3 | XP_005256682.1 | ||
KCNJ12 | XM_011523831.3 | c.116G>A | p.Arg39Gln | missense_variant | 3/3 | XP_011522133.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNJ12 | ENST00000583088.6 | c.116G>A | p.Arg39Gln | missense_variant | 3/3 | 1 | NM_021012.5 | ENSP00000463778 | P1 | |
KCNJ12 | ENST00000331718.5 | c.116G>A | p.Arg39Gln | missense_variant | 3/3 | 1 | ENSP00000328150 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 151152Hom.: 0 Cov.: 68
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00763 AC: 7668AN: 1004846Hom.: 0 Cov.: 203 AF XY: 0.00878 AC XY: 4418AN XY: 503178
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GnomAD4 genome AF: 0.000132 AC: 20AN: 151268Hom.: 0 Cov.: 68 AF XY: 0.000108 AC XY: 8AN XY: 73874
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
KCNJ12-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Benign
.;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MPC
ClinPred
T
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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