6-39207146-T-C

Variant names:

• chr6-39207146-T-C
• rs10947789
• NM_003740.4:c.187-11159A>G

Variant summary

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

The NM_003740.4(KCNK5):​c.187-11159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,196 control chromosomes in the GnomAD database, including 3,298 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 0.19 (3298 hom., cov: 32)
• Consequence: KCNK5 NM_003740.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 52 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 (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK5	NM_003740.4	c.187-11159A>G		intron_variant	Intron 1 of 4	ENST00000359534.4	NP_003731.1
KCNK5	XM_005249456.2	c.187-11159A>G		intron_variant	Intron 1 of 4		XP_005249513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK5	ENST00000359534.4	c.187-11159A>G		intron_variant	Intron 1 of 4	1	NM_003740.4	ENSP00000352527.3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28508 AN: 152078 Hom.: 3293 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.187 AC: 28517 AN: 152196 Hom.: 3298 Cov.: 32 AF XY: 0.192 AC XY: 14270 AN XY: 74380

African (AFR) AF: 0.0460 AC: 1911 AN: 41562

American (AMR) AF: 0.245 AC: 3740 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 817 AN: 3468

East Asian (EAS) AF: 0.207 AC: 1067 AN: 5158

South Asian (SAS) AF: 0.154 AC: 742 AN: 4810

European-Finnish (FIN) AF: 0.304 AC: 3225 AN: 10594

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16267 AN: 67994

Other (OTH) AF: 0.184 AC: 389 AN: 2112

Alfa AF: 0.219 Hom.: 11091

Bravo AF: 0.177

Asia WGS AF: 0.176 AC: 613 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	4.2
DANN	Benign	0.81
PhyloP100		-0.054
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: rs10947789; hg19: chr6-39174922;