dbSNP rs379643: 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:

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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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCNK10	NM_138317.3	MANE Select	c.*2125T>C	3_prime_UTR	Exon 7 of 7	NP_612190.1
KCNK10	NM_138318.3		c.*2125T>C	3_prime_UTR	Exon 7 of 7	NP_612191.1
KCNK10	NM_021161.5		c.*2125T>C	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.*2125T>C		3_prime_UTR	Exon 7 of 7	ENSP00000312811.5
	KCNK10	ENST00000340700.9	TSL:1	c.*2125T>C		3_prime_UTR	Exon 7 of 7	ENSP00000343104.5

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over