chr2-154855623-A-AT

Position:

• chr2-154855623-A-AT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002239.4(KCNJ3):​c.*310_*311insT 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 0.22 (3904 hom., cov: 19)
  • Exomes 𝑓: 0.15 (251 hom.)
• Consequence: KCNJ3 NM_002239.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ3	NM_002239.4	c.*310_*311insT		3_prime_UTR_variant	3/3	ENST00000295101.3	NP_002230.1
KCNJ3	NM_001260508.2	c.*891_*892insT		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	c.*310_*311insT		3_prime_UTR_variant	3/3	1	NM_002239.4	ENSP00000295101.2
KCNJ3	ENST00000544049.2	c.*891_*892insT		3_prime_UTR_variant	2/2	1		ENSP00000438410.1
KCNJ3	ENST00000651198.1	c.*310_*311insT		3_prime_UTR_variant	4/4			ENSP00000498639.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33560 AN: 150266 Hom.: 3898 Cov.: 19

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.100

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.153 AC: 2452 AN: 15980 Hom.: 251 Cov.: 0 AF XY: 0.152 AC XY: 1275 AN XY: 8386

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.0984

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.223 AC: 33582 AN: 150356 Hom.: 3904 Cov.: 19 AF XY: 0.227 AC XY: 16683 AN XY: 73414

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.213

Alfa AF: 0.0861 Hom.: 106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs5835552; hg19: chr2-155712135;