Genetic Variant KCNK10:c.*2125T>C (chr14-88183410-A-G) – 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.*2125T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,320 control chromosomes in the GnomAD database, including 7,985 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 0.31 ( 7977 hom., cov: 33)

Exomes 𝑓: 0.36 ( 8 hom. )

Consequence

KCNK10
NM_138317.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KCNK10	NM_138317.3 link	c.*2125T>C	3_prime_UTR_variant	Exon 7 of 7	ENST00000319231.10	NP_612190.1	P57789-3
KCNK10	NM_138318.3 link	c.*2125T>C	3_prime_UTR_variant	Exon 7 of 7		NP_612191.1	P57789-4
KCNK10	NM_021161.5 link	c.*2125T>C	3_prime_UTR_variant	Exon 7 of 7		NP_066984.1	P57789-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK10	ENST00000319231.10 link	c.*2125T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_138317.3	ENSP00000312811.5		P57789-3
KCNK10	ENST00000340700.9 link	c.*2125T>C		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000343104.5		P57789-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47805

AN:

152070

Hom.:

7969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.356

AC:

AN:

132

Hom.:

Cov.:

AF XY:

0.361

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.367

AC:

AN:

128

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.314

AC:

47833

AN:

152188

Hom.:

7977

Cov.:

AF XY:

0.311

AC XY:

23159

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.314

AC:

13019

AN:

41502

American (AMR)

AF:

0.205

AC:

3131

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

922

AN:

3466

East Asian (EAS)

AF:

0.566

AC:

2924

AN:

5168

South Asian (SAS)

AF:

0.363

AC:

1755

AN:

4830

European-Finnish (FIN)

AF:

0.281

AC:

2977

AN:

10606

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22136

AN:

67992

Other (OTH)

AF:

0.314

AC:

665

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1723

3445

5168

6890

8613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.320

Hom.:

4517

Bravo

AF:

0.311

Asia WGS

AF:

0.414

AC:

1438

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

(source)

DANN

Benign

0.72

PhyloP100

1.9

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