rs10456100

Positions:

• chr6-39215694-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK5	NM_003740.4	c.186+13232G>A		intron_variant		ENST00000359534.4
KCNK5	XM_005249456.2	c.186+13232G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK5	ENST00000359534.4	c.186+13232G>A		intron_variant		1	NM_003740.4	P1

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

Gnomad4 AFR AF: 0.0664

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.214

Alfa AF: 0.267 Hom.: 9303

Bravo AF: 0.202

Asia WGS AF: 0.247 AC: 858 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	7.6
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10456100; hg19: chr6-39183470;