Variant chr17-21415600-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_021012.5(KCNJ12):c.258C>A(p.Ile86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 0 hom., cov: 63)

Exomes 𝑓: 0.17 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ12
NM_021012.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.648

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:

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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 (BayesDel_noAF=-0.29).

BP6

Variant 17-21415600-C-A is Benign according to our data. Variant chr17-21415600-C-A is described in ClinVar as [Benign]. Clinvar id is 3058999.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.648 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNJ12	NM_021012.5 linkuse as main transcript	c.258C>A	p.Ile86=	synonymous_variant	3/3	ENST00000583088.6
KCNJ12	XM_005256625.6 linkuse as main transcript	c.258C>A	p.Ile86=	synonymous_variant	3/3
KCNJ12	XM_011523831.3 linkuse as main transcript	c.258C>A	p.Ile86=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ12	ENST00000583088.6 linkuse as main transcript	c.258C>A	p.Ile86=	synonymous_variant	3/3	1	NM_021012.5	P1
KCNJ12	ENST00000331718.5 linkuse as main transcript	c.258C>A	p.Ile86=	synonymous_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

32812

AN:

125250

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0826

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.277

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.165

AC:

146236

AN:

886016

Hom.:

Cov.:

208

AF XY:

0.172

AC XY:

75667

AN XY:

439180

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.468

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.367

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.262

AC:

32810

AN:

125362

Hom.:

Cov.:

AF XY:

0.272

AC XY:

16667

AN XY:

61378

show subpopulations

Gnomad4 AFR

AF:

0.0823

Gnomad4 AMR

AF:

0.366

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.468

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.403

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.212

Hom.:

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

Nov 01, 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

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.86

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