Variant 2-154699366-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_002239.4(KCNJ3):c.591C>T(p.Ser197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,612,170 control chromosomes in the GnomAD database, including 639 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.019 ( 28 hom., cov: 32)

Exomes 𝑓: 0.027 ( 611 hom. )

Consequence

KCNJ3
NM_002239.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.335

Variant links:

Genes affected

KCNJ3 (HGNC:6264): (potassium inwardly rectifying channel subfamily J member 3) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex that also couples to neurotransmitter receptors in the brain and whereby channel activation can inhibit action potential firing by hyperpolarizing the plasma membrane. These multimeric G-protein-gated inwardly-rectifying potassium (GIRK) channels may play a role in the pathophysiology of epilepsy, addiction, Down's syndrome, ataxia, and Parkinson's disease. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, May 2012]

KCNJ3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP7

Synonymous conserved (PhyloP=0.335 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0191 (2914/152226) while in subpopulation SAS AF= 0.0291 (140/4816). AF 95% confidence interval is 0.0271. There are 28 homozygotes in gnomad4. There are 1418 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNJ3	NM_002239.4 linkuse as main transcript	c.591C>T	p.Ser197=	synonymous_variant	1/3	ENST00000295101.3
KCNJ3	NM_001260509.2 linkuse as main transcript	c.591C>T	p.Ser197=	synonymous_variant	1/2
KCNJ3	NM_001260510.2 linkuse as main transcript	c.591C>T	p.Ser197=	synonymous_variant	1/1
KCNJ3	NM_001260508.2 linkuse as main transcript	c.591C>T	p.Ser197=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ3	ENST00000295101.3 linkuse as main transcript	c.591C>T	p.Ser197=	synonymous_variant	1/3	1	NM_002239.4	P1	P48549-1
KCNJ3	ENST00000544049.2 linkuse as main transcript	c.591C>T	p.Ser197=	synonymous_variant	1/2	1			P48549-2
KCNJ3	ENST00000651198.1 linkuse as main transcript	c.54C>T	p.Ser18=	synonymous_variant	2/4

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2914

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00567

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0195

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0282

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.0219

AC:

5464

AN:

249706

Hom.:

AF XY:

0.0223

AC XY:

3009

AN XY:

135156

show subpopulations

Gnomad AFR exome

AF:

0.00450

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.00744

Gnomad EAS exome

AF:

0.0314

Gnomad SAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0269

AC:

39299

AN:

1459944

Hom.:

611

Cov.:

AF XY:

0.0268

AC XY:

19431

AN XY:

726356

show subpopulations

Gnomad4 AFR exome

AF:

0.00385

Gnomad4 AMR exome

AF:

0.0118

Gnomad4 ASJ exome

AF:

0.00784

Gnomad4 EAS exome

AF:

0.0309

Gnomad4 SAS exome

AF:

0.0259

Gnomad4 FIN exome

AF:

0.0203

Gnomad4 NFE exome

AF:

0.0291

Gnomad4 OTH exome

AF:

0.0248

GnomAD4 genome

AF:

0.0191

AC:

2914

AN:

152226

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1418

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00566

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.0257

Gnomad4 SAS

AF:

0.0291

Gnomad4 FIN

AF:

0.0195

Gnomad4 NFE

AF:

0.0282

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0183

Hom.:

Bravo

AF:

0.0181

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0253

EpiControl

AF:

0.0242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.90

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over