rs17762565

Variant names:

• chr14-88190477-T-G
• rs17762565
• NM_138317.3:c.868+1747A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138317.3(KCNK10):​c.868+1747A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,154 control chromosomes in the GnomAD database, including 4,697 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 0.22 (4697 hom., cov: 32)
• Consequence: KCNK10 NM_138317.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138317.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK10	NM_138317.3	MANE Select	c.868+1747A>C		intron	N/A	NP_612190.1
	KCNK10	NM_138318.3		c.868+1747A>C		intron	N/A	NP_612191.1
	KCNK10	NM_021161.5		c.853+1747A>C		intron	N/A	NP_066984.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK10	ENST00000319231.10	TSL:1 MANE Select	c.868+1747A>C		intron	N/A	ENSP00000312811.5
	KCNK10	ENST00000312350.9	TSL:1	c.868+1747A>C		intron	N/A	ENSP00000310568.5
	KCNK10	ENST00000340700.9	TSL:1	c.853+1747A>C		intron	N/A	ENSP00000343104.5

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33140 AN: 152036 Hom.: 4696 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.218 AC: 33134 AN: 152154 Hom.: 4697 Cov.: 32 AF XY: 0.219 AC XY: 16274 AN XY: 74374

African (AFR) AF: 0.0635 AC: 2638 AN: 41538

American (AMR) AF: 0.219 AC: 3348 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3472

East Asian (EAS) AF: 0.0182 AC: 94 AN: 5174

South Asian (SAS) AF: 0.114 AC: 548 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3624 AN: 10584

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20996 AN: 67970

Other (OTH) AF: 0.210 AC: 443 AN: 2110

Alfa AF: 0.253 Hom.: 917

Bravo AF: 0.202

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		-0.13
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: rs17762565; hg19: chr14-88656821;