chr6-39215694-C-T

Variant names:

• chr6-39215694-C-T
• rs10456100
• NM_003740.4:c.186+13232G>A

Variant summary

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

The NM_003740.4(KCNK5):​c.186+13232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,210 control chromosomes in the GnomAD database, including 3,901 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 0.21 (3901 hom., cov: 33)
• Consequence: KCNK5 NM_003740.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 27 publications found

Genes affected

KCNK5 (HGNC:6280): (potassium two pore domain channel subfamily K member 5) This gene encodes one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. The message for this gene is mainly expressed in the cortical distal tubules and collecting ducts of the kidney. The protein is highly sensitive to external pH and this, in combination with its expression pattern, suggests it may play an important role in renal potassium transport. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003740.4. 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
	KCNK5	NM_003740.4	MANE Select	c.186+13232G>A		intron	N/A	NP_003731.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK5	ENST00000359534.4	TSL:1 MANE Select	c.186+13232G>A		intron	N/A	ENSP00000352527.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31408 AN: 152092 Hom.: 3896 Cov.: 33

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.206 AC: 31430 AN: 152210 Hom.: 3901 Cov.: 33 AF XY: 0.205 AC XY: 15289 AN XY: 74424

African (AFR) AF: 0.0664 AC: 2760 AN: 41554

American (AMR) AF: 0.228 AC: 3493 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3470

East Asian (EAS) AF: 0.178 AC: 920 AN: 5174

South Asian (SAS) AF: 0.314 AC: 1515 AN: 4826

European-Finnish (FIN) AF: 0.205 AC: 2174 AN: 10590

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19096 AN: 67990

Other (OTH) AF: 0.214 AC: 453 AN: 2114

Alfa AF: 0.252 Hom.: 13979

Bravo AF: 0.202

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.63
PhyloP100		0.33
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: rs10456100; hg19: chr6-39183470;