rs379643

chr14-88183410-A-Gchr14-88183410-A-T

Variant summary

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

The NM_138317.3(KCNK10):c.*2125T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,320 control chromosomes in the GnomAD database, including 7,985 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 0.31 (7977 hom., cov: 33)
  • Exomes 𝑓: 0.36 (8 hom.)
• Consequence: KCNK10 NM_138317.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

Genes affected

KCNK10 (HGNC:6273): (potassium two pore domain channel subfamily K member 10) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK10	NM_138317.3	c.*2125T>C		3_prime_UTR_variant	7/7	ENST00000319231.10
KCNK10	NM_021161.5	c.*2125T>C		3_prime_UTR_variant	7/7
KCNK10	NM_138318.3	c.*2125T>C		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK10	ENST00000319231.10	c.*2125T>C		3_prime_UTR_variant	7/7	1	NM_138317.3	P1
KCNK10	ENST00000340700.9	c.*2125T>C		3_prime_UTR_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47805 AN: 152070 Hom.: 7969 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.356 AC: 47 AN: 132 Hom.: 8 Cov.: 0 AF XY: 0.361 AC XY: 26 AN XY: 72

Gnomad4 EAS exome AF: 0.367

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.314 AC: 47833 AN: 152188 Hom.: 7977 Cov.: 33 AF XY: 0.311 AC XY: 23159 AN XY: 74418

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.314

Alfa AF: 0.319 Hom.: 4064

Bravo AF: 0.311

Asia WGS AF: 0.414 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	10
Dann	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs379643; hg19: chr14-88649754;