2-26692756-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_002246.3(KCNK3):c.-120G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 465,024 control chromosomes in the GnomAD database, including 80,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (20193 hom., cov: 30)
  • Exomes 𝑓: 0.61 (60667 hom.)
• Consequence: KCNK3 NM_002246.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.398

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=-0.35).
• BP6: Variant 2-26692756-G-T is Benign according to our data. Variant chr2-26692756-G-T is described in ClinVar as [Benign]. Clinvar id is 1235279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK3	NM_002246.3	c.-120G>T		5_prime_UTR_variant	1/2	ENST00000302909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK3	ENST00000302909.4	c.-120G>T		5_prime_UTR_variant	1/2	1	NM_002246.3	P1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 72505 AN: 146186 Hom.: 20180 Cov.: 30

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.587

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.610 AC: 194573 AN: 318728 Hom.: 60667 Cov.: 5 AF XY: 0.610 AC XY: 92685 AN XY: 151824

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.633

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.628

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.496 AC: 72550 AN: 146296 Hom.: 20193 Cov.: 30 AF XY: 0.493 AC XY: 35118 AN XY: 71180

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.546

Alfa AF: 0.397 Hom.: 1104

Bravo AF: 0.496

Asia WGS AF: 0.444 AC: 1226 AN: 2756

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	17
Dann	Benign	0.94

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: rs12476527; hg19: chr2-26915624;