2-154698683-T-TCCCCC

Position:

• chr2-154698683-T-TCCCCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000544049.2(KCNJ3):​c.-93_-92insCCCCC 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 0.000017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00064 (4 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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ3	NM_002239.4	c.-93_-92insCCCCC		upstream_gene_variant		ENST00000295101.3	NP_002230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ3	ENST00000544049.2	c.-93_-92insCCCCC		5_prime_UTR_variant	1/2	1		ENSP00000438410.1
KCNJ3	ENST00000651198.1	c.-42-588_-42-587insCCCCC		intron_variant				ENSP00000498639.1
KCNJ3	ENST00000295101.3	c.-93_-92insCCCCC		upstream_gene_variant		1	NM_002239.4	ENSP00000295101.2

Frequencies

GnomAD3 genomes AF: 0.0000175 AC: 2 AN: 114456 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000297

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000174

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000639 AC: 46 AN: 71944 Hom.: 4 Cov.: 2 AF XY: 0.000484 AC XY: 19 AN XY: 39226

Gnomad4 AFR exome AF: 0.000318

Gnomad4 AMR exome AF: 0.00122

Gnomad4 ASJ exome AF: 0.00123

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000123

Gnomad4 FIN exome AF: 0.000204

Gnomad4 NFE exome AF: 0.00101

Gnomad4 OTH exome AF: 0.000742

GnomAD4 genome AF: 0.0000175 AC: 2 AN: 114456 Hom.: 0 Cov.: 0 AF XY: 0.0000182 AC XY: 1 AN XY: 55026

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000297

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000174

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;