rs5835535

chr2-154698683-T-TCchr2-154698683-T-TCCCchr2-154698683-T-TCCCCchr2-154698683-T-TCCCCCchr2-154698683-T-TCCCCCCC

Variant summary

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

The ENST00000544049.2(KCNJ3):c.-88dup 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ3	NM_002239.4			upstream_gene_variant		ENST00000295101.3
KCNJ3	NM_001260508.2			upstream_gene_variant
KCNJ3	NM_001260509.2			upstream_gene_variant
KCNJ3	NM_001260510.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ3	ENST00000544049.2	c.-88dup		5_prime_UTR_variant	1/2	1
KCNJ3	ENST00000651198.1	c.-42-583dup		intron_variant
KCNJ3	ENST00000295101.3			upstream_gene_variant		1	NM_002239.4	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 49747 AN: 114190 Hom.: 9876 Cov.: 0

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.: 2 AF XY: 0.297 AC XY: 11595 AN XY: 39026

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.0215

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.436 AC: 49759 AN: 114240 Hom.: 9877 Cov.: 0 AF XY: 0.437 AC XY: 24008 AN XY: 54932

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.412

Alfa AF: 0.349 Hom.: 666

Asia WGS AF: 0.212 AC: 737 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs5835535; hg19: chr2-155555195;