NM_138317.3:c.*873A>G

Variant names:

• chr14-88184662-T-C
• rs411627
• NM_138317.3:c.*873A>G

Variant summary

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

The NM_138317.3(KCNK10):​c.*873A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,238 control chromosomes in the GnomAD database, including 7,425 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 0.30 (7414 hom., cov: 32)
  • Exomes 𝑓: 0.37 (11 hom.)
• Consequence: KCNK10 NM_138317.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 6 publications found

Genes affected

KCNK10 (HGNC:6273): (potassium two pore domain channel subfamily K member 10) 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, and is stimulated strongly by arachidonic acid and to a lesser degree by membrane stretching, intracellular acidification, and general anaesthetics. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138317.3. 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
	KCNK10	NM_138317.3	MANE Select	c.*873A>G		3_prime_UTR	Exon 7 of 7	NP_612190.1
	KCNK10	NM_138318.3		c.*873A>G		3_prime_UTR	Exon 7 of 7	NP_612191.1
	KCNK10	NM_021161.5		c.*873A>G		3_prime_UTR	Exon 7 of 7	NP_066984.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK10	ENST00000319231.10	TSL:1 MANE Select	c.*873A>G		3_prime_UTR	Exon 7 of 7	ENSP00000312811.5
	KCNK10	ENST00000340700.9	TSL:1	c.*873A>G		3_prime_UTR	Exon 7 of 7	ENSP00000343104.5
	KCNK10	ENST00000312350.9	TSL:1	c.*873A>G		downstream_gene	N/A	ENSP00000310568.5

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46086 AN: 151978 Hom.: 7406 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.371 AC: 52 AN: 140 Hom.: 11 Cov.: 0 AF XY: 0.388 AC XY: 31 AN XY: 80

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.360 AC: 49 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.303 AC: 46115 AN: 152098 Hom.: 7414 Cov.: 32 AF XY: 0.300 AC XY: 22321 AN XY: 74366

African (AFR) AF: 0.308 AC: 12783 AN: 41482

American (AMR) AF: 0.200 AC: 3053 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2854 AN: 5162

South Asian (SAS) AF: 0.337 AC: 1624 AN: 4814

European-Finnish (FIN) AF: 0.273 AC: 2894 AN: 10594

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21042 AN: 67972

Other (OTH) AF: 0.306 AC: 646 AN: 2114

Alfa AF: 0.309 Hom.: 31528

Bravo AF: 0.301

Asia WGS AF: 0.396 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs411627; hg19: chr14-88651006;