Variant chr17-21415448-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_021012.5(KCNJ12):c.106G>T(p.Val36Leu) variant causes a missense change. The variant allele was found at a frequency of 0.184 in 135,898 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 (★).

Frequency

Genomes: 𝑓 0.18 ( 0 hom., cov: 68)

Exomes 𝑓: 0.12 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ12
NM_021012.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.31

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 Benign. Variant got -13 ACMG points.

PP2

Missense variant where missense usually causes diseases, KCNJ12

BP4

Computational evidence support a benign effect (MetaRNN=0.0021412075).

BP6

Variant 17-21415448-G-T is Benign according to our data. Variant chr17-21415448-G-T is described in ClinVar as [Benign]. Clinvar id is 3059989.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNJ12	NM_021012.5 linkuse as main transcript	c.106G>T	p.Val36Leu	missense_variant	3/3	ENST00000583088.6
KCNJ12	XM_005256625.6 linkuse as main transcript	c.106G>T	p.Val36Leu	missense_variant	3/3
KCNJ12	XM_011523831.3 linkuse as main transcript	c.106G>T	p.Val36Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ12	ENST00000583088.6 linkuse as main transcript	c.106G>T	p.Val36Leu	missense_variant	3/3	1	NM_021012.5	P1
KCNJ12	ENST00000331718.5 linkuse as main transcript	c.106G>T	p.Val36Leu	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

25016

AN:

135780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.0940

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.177

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.119

AC:

133809

AN:

1124048

Hom.:

Cov.:

200

AF XY:

0.118

AC XY:

65991

AN XY:

561308

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.0689

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.0645

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.184

AC:

25051

AN:

135898

Hom.:

Cov.:

AF XY:

0.180

AC XY:

11993

AN XY:

66560

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.179

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.196

Hom.:

997

ExAC

AF:

0.0913

AC:

11089

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 18, 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

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

0.053

FATHMM_MKL

Uncertain

0.92

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.12

N;N

MutationTaster

Benign

0.78

D;D

PrimateAI

Uncertain

0.73

Sift4G

Benign

0.80

T;T

Polyphen

0.0

B;B

Vest4

0.079

MutPred

0.53

Loss of methylation at K35 (P = 0.0359);Loss of methylation at K35 (P = 0.0359);

MPC

0.081

ClinPred

0.0065

GERP RS

4.3

Varity_R

0.083

gMVP

0.50

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