rs13394970

Variant names:

• chr2-26706414-T-G
• rs13394970
• NM_002246.3:c.283+13256T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

KCNK3 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• pulmonary hypertension, primary, 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• heritable pulmonary arterial hypertension

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNK3	NM_002246.3	c.283+13256T>G		intron_variant	Intron 1 of 1	ENST00000302909.4	NP_002237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK3	ENST00000302909.4	c.283+13256T>G		intron_variant	Intron 1 of 1	1	NM_002246.3	ENSP00000306275.3

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

African (AFR) AF: 0.537 AC: 22265 AN: 41444

American (AMR) AF: 0.693 AC: 10589 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2104 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1292 AN: 5136

South Asian (SAS) AF: 0.536 AC: 2580 AN: 4812

European-Finnish (FIN) AF: 0.531 AC: 5607 AN: 10568

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41093 AN: 67896

Other (OTH) AF: 0.612 AC: 1293 AN: 2114

Alfa AF: 0.601 Hom.: 9236

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
PhyloP100		0.54
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: rs13394970; hg19: chr2-26929282;