Variant 2-154855301-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002239.4(KCNJ3):c.1494T>C(p.Asp498=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,600,582 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 20 hom. )

Consequence

KCNJ3
NM_002239.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.214

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 2-154855301-T-C is Benign according to our data. Variant chr2-154855301-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 710586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ3	NM_002239.4 linkuse as main transcript	c.1494T>C	p.Asp498=	synonymous_variant	3/3	ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2 linkuse as main transcript	c.*569T>C		3_prime_UTR_variant	2/2		NP_001247437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ3	ENST00000295101.3 linkuse as main transcript	c.1494T>C	p.Asp498=	synonymous_variant	3/3	1	NM_002239.4	ENSP00000295101	P1	P48549-1
KCNJ3	ENST00000544049.2 linkuse as main transcript	c.*569T>C		3_prime_UTR_variant	2/2	1		ENSP00000438410		P48549-2
KCNJ3	ENST00000651198.1 linkuse as main transcript	c.957T>C	p.Asp319=	synonymous_variant	4/4			ENSP00000498639

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

539

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00575

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00317

AC:

736

AN:

232314

Hom.:

AF XY:

0.00295

AC XY:

373

AN XY:

126560

show subpopulations

Gnomad AFR exome

AF:

0.000929

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000547

Gnomad FIN exome

AF:

0.00181

Gnomad NFE exome

AF:

0.00505

Gnomad OTH exome

AF:

0.00379

GnomAD4 exome

AF:

0.00412

AC:

5967

AN:

1448318

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

2831

AN XY:

720812

show subpopulations

Gnomad4 AFR exome

AF:

0.000861

Gnomad4 AMR exome

AF:

0.00362

Gnomad4 ASJ exome

AF:

0.000785

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000693

Gnomad4 FIN exome

AF:

0.00200

Gnomad4 NFE exome

AF:

0.00488

Gnomad4 OTH exome

AF:

0.00354

GnomAD4 genome

AF:

0.00353

AC:

538

AN:

152264

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

243

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00575

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00345

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	KCNJ3: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.1

DANN

Benign

0.62

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