chr6-39305650-C-G

Variant names:

• chr6-39305650-C-G
• rs10807204
• NM_031460.4:c.353-995G>C

Variant summary

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

The NM_031460.4(KCNK17):​c.353-995G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,198 control chromosomes in the GnomAD database, including 3,188 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 0.18 (3188 hom., cov: 32)
• Consequence: KCNK17 NM_031460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 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.353-995G>C		intron	N/A	NP_113648.2
	KCNK17	NM_001135111.2		c.353-995G>C		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.353-995G>C		intron	N/A	ENSP00000362328.4
	KCNK17	ENST00000503878.1	TSL:1	n.458-995G>C		intron	N/A
	KCNK17	ENST00000453413.2	TSL:5	c.353-995G>C		intron	N/A	ENSP00000401271.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27582 AN: 152080 Hom.: 3184 Cov.: 32

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.181 AC: 27595 AN: 152198 Hom.: 3188 Cov.: 32 AF XY: 0.186 AC XY: 13841 AN XY: 74408

African (AFR) AF: 0.0437 AC: 1816 AN: 41560

American (AMR) AF: 0.225 AC: 3446 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3470

East Asian (EAS) AF: 0.388 AC: 2006 AN: 5170

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4820

European-Finnish (FIN) AF: 0.269 AC: 2845 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14781 AN: 67980

Other (OTH) AF: 0.188 AC: 398 AN: 2112

Alfa AF: 0.108 Hom.: 186

Bravo AF: 0.173

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.43
PhyloP100		0.58
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: rs10807204; hg19: chr6-39273426;