Genetic Variant KCNJ3:c.*310_*311insTAT (chr2-154855623-A-ATAT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002239.4(KCNJ3):c.*310_*311insTAT variant causes a 3 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 0.000053 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

KCNJ3
NM_002239.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ3	NM_002239.4 link	c.310_311insTAT		3_prime_UTR_variant	Exon 3 of 3	ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2 link	c.891_892insTAT		3_prime_UTR_variant	Exon 2 of 2		NP_001247437.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
KCNJ3	ENST00000295101.3 link	c.310_311insTAT	3_prime_UTR_variant	Exon 3 of 3	1	NM_002239.4	ENSP00000295101.2
KCNJ3	ENST00000544049.2 link	c.891_892insTAT	3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000438410.1
KCNJ3	ENST00000651198.1 link	c.310_311insTAT	3_prime_UTR_variant	Exon 4 of 4			ENSP00000498639.1

Frequencies

GnomAD3 genomes

AF:

0.0000532

AC:

AN:

150392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000740

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000624

AC:

AN:

16018

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

8408

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

410

American (AMR)

AF:

0.000505

AC:

AN:

1980

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

376

East Asian (EAS)

AF:

0.00

AC:

AN:

770

South Asian (SAS)

AF:

0.00

AC:

AN:

1362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

9500

Other (OTH)

AF:

0.00

AC:

AN:

816

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000532

AC:

AN:

150482

Hom.:

Cov.:

AF XY:

0.0000816

AC XY:

AN XY:

73498

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41170

American (AMR)

AF:

0.00

AC:

AN:

15080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.000418

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000740

AC:

AN:

67584

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000439

Hom.:

106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over