Genetic Variant KCNK10:c.*873A>G (chr14-88184662-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

Publications

6 publications found

Variant links:

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]

KCNK10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
KCNK10	NM_138317.3 link	c.*873A>G	3_prime_UTR_variant	Exon 7 of 7	ENST00000319231.10	NP_612190.1
KCNK10	NM_138318.3 link	c.*873A>G	3_prime_UTR_variant	Exon 7 of 7		NP_612191.1
KCNK10	NM_021161.5 link	c.*873A>G	3_prime_UTR_variant	Exon 7 of 7		NP_066984.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
KCNK10	ENST00000319231.10 link	c.*873A>G	3_prime_UTR_variant	Exon 7 of 7	1	NM_138317.3	ENSP00000312811.5
KCNK10	ENST00000340700.9 link	c.*873A>G	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000343104.5
KCNK10	ENST00000312350.9 link	c.*873A>G	downstream_gene_variant		1		ENSP00000310568.5

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46086

AN:

151978

Hom.:

7406

Cov.:

show subpopulations

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:

AN:

140

Hom.:

Cov.:

AF XY:

0.388

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.360

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.303

AC:

46115

AN:

152098

Hom.:

7414

Cov.:

AF XY:

0.300

AC XY:

22321

AN XY:

74366

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.310

AC:

21042

AN:

67972

Other (OTH)

AF:

0.306

AC:

646

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1666

3333

4999

6666

8332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.4

(source)

DANN

Benign

0.58

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over