2-26692748-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002246.3(KCNK3):c.-128G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00639 in 390,026 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0068 (11 hom.)
• Consequence: KCNK3 NM_002246.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.279

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 2-26692748-G-C is Benign according to our data. Variant chr2-26692748-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2504974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 848 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK3	NM_002246.3	c.-128G>C		5_prime_UTR_variant	1/2	ENST00000302909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK3	ENST00000302909.4	c.-128G>C		5_prime_UTR_variant	1/2	1	NM_002246.3	P1

Frequencies

GnomAD3 genomes AF: 0.00578 AC: 848 AN: 146808 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00581

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00355

Gnomad FIN AF: 0.00127

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.00880

Gnomad OTH AF: 0.00841

GnomAD4 exome AF: 0.00676 AC: 1644 AN: 243110 Hom.: 11 Cov.: 5 AF XY: 0.00678 AC XY: 793 AN XY: 116978

Gnomad4 AFR exome AF: 0.00178

Gnomad4 AMR exome AF: 0.00581

Gnomad4 ASJ exome AF: 0.0268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00577

Gnomad4 FIN exome AF: 0.00714

Gnomad4 NFE exome AF: 0.00679

Gnomad4 OTH exome AF: 0.00628

GnomAD4 genome AF: 0.00577 AC: 848 AN: 146916 Hom.: 4 Cov.: 31 AF XY: 0.00576 AC XY: 412 AN XY: 71560

Gnomad4 AFR AF: 0.00110

Gnomad4 AMR AF: 0.00580

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00355

Gnomad4 FIN AF: 0.00127

Gnomad4 NFE AF: 0.00880

Gnomad4 OTH AF: 0.00832

Alfa AF: 0.00999 Hom.: 4

Bravo AF: 0.00583

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	14
Dann	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs868836533; hg19: chr2-26915616;