chr6-39207146-T-C

Position:

• chr6-39207146-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK5	NM_003740.4	c.187-11159A>G		intron_variant		ENST00000359534.4	NP_003731.1
KCNK5	XM_005249456.2	c.187-11159A>G		intron_variant			XP_005249513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK5	ENST00000359534.4	c.187-11159A>G		intron_variant		1	NM_003740.4	ENSP00000352527	P1

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

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.184

Alfa AF: 0.225 Hom.: 4564

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

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: rs10947789; hg19: chr6-39174922;