Genetic Variant KCNJ3:c.-88_-87insCCCCCCCCCCCC (chr2-154698683-T-TCCCCCCCCCCCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000544049.2(KCNJ3):c.-88_-87insCCCCCCCCCCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

KCNJ3
ENST00000544049.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.896

Publications

0 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:

Genome browser will be placed here

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: Uncertain_significance. The variant received 0 ACMG points.

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_-92insCCCCCCCCCCCC	upstream_gene	N/A	NP_002230.1	P48549-1
KCNJ3	NM_001260509.2		c.-93_-92insCCCCCCCCCCCC	upstream_gene	N/A	NP_001247438.1	D2X9V0
KCNJ3	NM_001260510.2		c.-93_-92insCCCCCCCCCCCC	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.-88_-87insCCCCCCCCCCCC	5_prime_UTR	Exon 1 of 2	ENSP00000438410.1	P48549-2
KCNJ3	ENST00000651198.1		c.-42-583_-42-582insCCCCCCCCCCCC	intron	N/A	ENSP00000498639.1	A0A494C0M7
ENSG00000287900	ENST00000803267.1		n.769_770insGGGGGGGGGGGG	non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000278

AC:

AN:

71950

Hom.:

Cov.:

AF XY:

0.0000510

AC XY:

AN XY:

39228

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:

3144

American (AMR)

AF:

0.00

AC:

AN:

5732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

812

East Asian (EAS)

AF:

0.00

AC:

AN:

4884

South Asian (SAS)

AF:

0.000122

AC:

AN:

8164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1268

European-Non Finnish (NFE)

AF:

0.0000327

AC:

AN:

30548

Other (OTH)

AF:

0.00

AC:

AN:

2694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.90

Splicing

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over