Variant 17-21415475-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BP4

The NM_021012.5(KCNJ12):c.133C>T(p.Arg45Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0016 in 152,226 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 71)

Exomes 𝑓: 0.00012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ12
NM_021012.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

Variant links:

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]

KCNJ12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 10: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.33368573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ12	NM_021012.5 linkuse as main transcript	c.133C>T	p.Arg45Cys	missense_variant	3/3	ENST00000583088.6	NP_066292.2	Q14500
KCNJ12	XM_005256625.6 linkuse as main transcript	c.133C>T	p.Arg45Cys	missense_variant	3/3		XP_005256682.1	Q14500
KCNJ12	XM_011523831.3 linkuse as main transcript	c.133C>T	p.Arg45Cys	missense_variant	3/3		XP_011522133.1	Q14500

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ12	ENST00000583088.6 linkuse as main transcript	c.133C>T	p.Arg45Cys	missense_variant	3/3	1	NM_021012.5	ENSP00000463778.1		Q14500
KCNJ12	ENST00000331718.5 linkuse as main transcript	c.133C>T	p.Arg45Cys	missense_variant	3/3	1		ENSP00000328150.5		Q14500

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

241

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00191

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000117

AC:

171

AN:

1461064

Hom.:

Cov.:

251

AF XY:

0.000111

AC XY:

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00277

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00160

AC:

243

AN:

152226

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00531

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000277

Hom.:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

T;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

1.0

.;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.33

T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Pathogenic

4.0

H;H

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-7.0

.;D

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.93

MVP

0.61

MPC

0.53

ClinPred

0.98

GERP RS

5.2

Varity_R

0.81

gMVP

0.97

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over