rs13394970

Positions:

• chr2-26706414-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002246.3(KCNK3):​c.283+13256T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,932 control chromosomes in the GnomAD database, including 25,758 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25758 hom., cov: 32)
• Consequence: KCNK3 NM_002246.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541

Genes affected

KCNK3 (HGNC:6278): (potassium two pore domain channel subfamily K member 3) This gene encodes a member of the superfamily of potassium channel proteins that contain two pore-forming P domains. The encoded protein is an outwardly rectifying channel that is sensitive to changes in extracellular pH and is inhibited by extracellular acidification. Also referred to as an acid-sensitive potassium channel, it is activated by the anesthetics halothane and isoflurane. Although three transcripts are detected in northern blots, there is currently no sequence available to confirm transcript variants for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK3	NM_002246.3	c.283+13256T>G		intron_variant		ENST00000302909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK3	ENST00000302909.4	c.283+13256T>G		intron_variant		1	NM_002246.3	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87521 AN: 151814 Hom.: 25713 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.608

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.577 AC: 87616 AN: 151932 Hom.: 25758 Cov.: 32 AF XY: 0.572 AC XY: 42475 AN XY: 74256

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.612

Alfa AF: 0.598 Hom.: 5475

Bravo AF: 0.589

Asia WGS AF: 0.462 AC: 1608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.4
DANN	Benign	0.73

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: rs13394970; hg19: chr2-26929282;