Variant 17-21415470-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_StrongBP6_Moderate

The NM_021012.5(KCNJ12):c.128G>A(p.Arg43His) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 0 hom., cov: 68)

Exomes 𝑓: 0.50 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ12
NM_021012.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.82

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 Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, KCNJ12

BP4

Computational evidence support a benign effect (MetaRNN=0.0019116104).

BP6

Variant 17-21415470-G-A is Benign according to our data. Variant chr17-21415470-G-A is described in ClinVar as [Benign]. Clinvar id is 3060108.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNJ12	NM_021012.5 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	3/3	ENST00000583088.6
KCNJ12	XM_005256625.6 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	3/3
KCNJ12	XM_011523831.3 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ12	ENST00000583088.6 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	3/3	1	NM_021012.5	P1
KCNJ12	ENST00000331718.5 linkuse as main transcript	c.128G>A	p.Arg43His	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

76125

AN:

152270

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.500

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.500

AC:

726953

AN:

1454152

Hom.:

Cov.:

227

AF XY:

0.500

AC XY:

361305

AN XY:

722746

show subpopulations

Gnomad4 AFR exome

AF:

0.499

Gnomad4 AMR exome

AF:

0.499

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.500

AC:

76184

AN:

152388

Hom.:

Cov.:

AF XY:

0.500

AC XY:

37254

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.500

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.500

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.481

Hom.:

ExAC

AF:

0.471

AC:

57158

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KCNJ12-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

T;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.82

Sift4G

Uncertain

0.052

T;T

Polyphen

0.18

B;B

Vest4

0.63

MPC

0.11

ClinPred

0.048

GERP RS

4.4

Varity_R

0.32

gMVP

0.72

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