2-154855623-A-AT

Variant names:

• chr2-154855623-A-AT
• rs5835552
• NM_002239.4:c.*310_*311insT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	NM_002239.4	MANE Select	c.*310_*311insT		3_prime_UTR	Exon 3 of 3	NP_002230.1	P48549-1
	KCNJ3	NM_001260508.2		c.*891_*892insT		3_prime_UTR	Exon 2 of 2	NP_001247437.1	P48549-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	ENST00000295101.3	TSL:1 MANE Select	c.*310_*311insT		3_prime_UTR	Exon 3 of 3	ENSP00000295101.2	P48549-1
	KCNJ3	ENST00000544049.2	TSL:1	c.*891_*892insT		3_prime_UTR	Exon 2 of 2	ENSP00000438410.1	P48549-2
	KCNJ3	ENST00000651198.1		c.*310_*311insT		3_prime_UTR	Exon 4 of 4	ENSP00000498639.1	A0A494C0M7

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

African (AFR) AF: 0.102 AC: 42 AN: 410

American (AMR) AF: 0.199 AC: 392 AN: 1970

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 37 AN: 376

East Asian (EAS) AF: 0.230 AC: 175 AN: 762

South Asian (SAS) AF: 0.147 AC: 200 AN: 1360

European-Finnish (FIN) AF: 0.202 AC: 154 AN: 764

Middle Eastern (MID) AF: 0.111 AC: 4 AN: 36

European-Non Finnish (NFE) AF: 0.139 AC: 1323 AN: 9488

Other (OTH) AF: 0.154 AC: 125 AN: 814

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

African (AFR) AF: 0.192 AC: 7886 AN: 41140

American (AMR) AF: 0.268 AC: 4034 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3462

East Asian (EAS) AF: 0.357 AC: 1827 AN: 5116

South Asian (SAS) AF: 0.215 AC: 1027 AN: 4780

European-Finnish (FIN) AF: 0.271 AC: 2708 AN: 9976

Middle Eastern (MID) AF: 0.105 AC: 30 AN: 286

European-Non Finnish (NFE) AF: 0.219 AC: 14803 AN: 67548

Other (OTH) AF: 0.213 AC: 444 AN: 2084

Alfa AF: 0.0861 Hom.: 106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5835552; hg19: chr2-155712135;