rs12195376

Variant names:

• chr6-39305090-C-T
• rs12195376
• NM_031460.4:c.353-435G>A

Variant summary

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

The NM_031460.4(KCNK17):​c.353-435G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,256 control chromosomes in the GnomAD database, including 1,388 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 0.12 (1388 hom., cov: 33)
• Consequence: KCNK17 NM_031460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 1 publications found

Genes affected

KCNK17 (HGNC:14465): (potassium two pore domain channel subfamily K member 17) 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. This gene is activated at alkaline pH. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

KCNK17 Gene-Disease associations (from GenCC):

• heart conduction disease

  Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031460.4. 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
	KCNK17	NM_031460.4	MANE Select	c.353-435G>A		intron	N/A	NP_113648.2
	KCNK17	NM_001135111.2		c.353-435G>A		intron	N/A	NP_001128583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK17	ENST00000373231.9	TSL:1 MANE Select	c.353-435G>A		intron	N/A	ENSP00000362328.4
	KCNK17	ENST00000503878.1	TSL:1	n.458-435G>A		intron	N/A
	KCNK17	ENST00000453413.2	TSL:5	c.353-435G>A		intron	N/A	ENSP00000401271.2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18608 AN: 152138 Hom.: 1385 Cov.: 33

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.122 AC: 18615 AN: 152256 Hom.: 1388 Cov.: 33 AF XY: 0.123 AC XY: 9186 AN XY: 74430

African (AFR) AF: 0.0318 AC: 1322 AN: 41566

American (AMR) AF: 0.197 AC: 3017 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3470

East Asian (EAS) AF: 0.111 AC: 572 AN: 5154

South Asian (SAS) AF: 0.145 AC: 701 AN: 4828

European-Finnish (FIN) AF: 0.143 AC: 1513 AN: 10614

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10510 AN: 68010

Other (OTH) AF: 0.135 AC: 285 AN: 2116

Alfa AF: 0.141 Hom.: 245

Bravo AF: 0.121

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.23
PhyloP100		0.088
Mutation Taster		=99/1	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: rs12195376; hg19: chr6-39272866;