Genetic Variant ENST00000544049.2:c.-88dupC (chr2-154698683-T-TC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000544049.2(KCNJ3):c.-88dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 9877 hom., cov: 0)

Exomes 𝑓: 0.30 ( 4747 hom. )

Consequence

KCNJ3
ENST00000544049.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.896

Publications

3 publications found

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:

ENSG00000287900 (HGNC:):

ENSG00000287900 links:

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new If you want to explore the variant's impact on the transcript ENST00000544049.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000544049.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ3	NM_002239.4	MANE Select	c.-93_-92insC	upstream_gene	N/A	NP_002230.1	P48549-1
KCNJ3	NM_001260509.2		c.-93_-92insC	upstream_gene	N/A	NP_001247438.1	D2X9V0
KCNJ3	NM_001260510.2		c.-93_-92insC	upstream_gene	N/A	NP_001247439.1	D2XBF0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ3	ENST00000544049.2	TSL:1	c.-88dupC	5_prime_UTR	Exon 1 of 2	ENSP00000438410.1	P48549-2
KCNJ3	ENST00000651198.1		c.-42-583dupC	intron	N/A	ENSP00000498639.1	A0A494C0M7
ENSG00000287900	ENST00000803267.1		n.769dupG	non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

49747

AN:

114190

Hom.:

9876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.625

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.0423

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.586

Gnomad MID

AF:

0.346

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.411

GnomAD4 exome

AF:

0.295

AC:

21126

AN:

71610

Hom.:

4747

Cov.:

AF XY:

0.297

AC XY:

11595

AN XY:

39026

show subpopulations

African (AFR)

AF:

0.138

AC:

431

AN:

3134

American (AMR)

AF:

0.247

AC:

1409

AN:

5702

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

223

AN:

808

East Asian (EAS)

AF:

0.0215

AC:

105

AN:

4880

South Asian (SAS)

AF:

0.203

AC:

1648

AN:

8118

European-Finnish (FIN)

AF:

0.482

AC:

7055

AN:

14642

Middle Eastern (MID)

AF:

0.246

AC:

310

AN:

1260

European-Non Finnish (NFE)

AF:

0.301

AC:

9159

AN:

30380

Other (OTH)

AF:

0.293

AC:

786

AN:

2686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

479

958

1437

1916

2395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.436

AC:

49759

AN:

114240

Hom.:

9877

Cov.:

AF XY:

0.437

AC XY:

24008

AN XY:

54932

show subpopulations

African (AFR)

AF:

0.274

AC:

7269

AN:

26498

American (AMR)

AF:

0.457

AC:

5117

AN:

11208

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1277

AN:

2866

East Asian (EAS)

AF:

0.0417

AC:

113

AN:

2710

South Asian (SAS)

AF:

0.409

AC:

1369

AN:

3350

European-Finnish (FIN)

AF:

0.586

AC:

4548

AN:

7758

Middle Eastern (MID)

AF:

0.348

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.504

AC:

28832

AN:

57226

Other (OTH)

AF:

0.412

AC:

653

AN:

1586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1363

2727

4090

5454

6817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.349

Hom.:

666

Asia WGS

AF:

0.212

AC:

737

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.90

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over