Genetic Variant NM_138317.3:c.877G>C (chr14-88188101-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138317.3(KCNK10):c.877G>C(p.Ala293Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A293T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KCNK10
NM_138317.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.556

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19845974).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNK10	NM_138317.3	MANE Select	c.877G>C	p.Ala293Pro	missense	Exon 6 of 7	NP_612190.1	P57789-3
KCNK10	NM_138318.3		c.877G>C	p.Ala293Pro	missense	Exon 6 of 7	NP_612191.1	P57789-4
KCNK10	NM_021161.5		c.862G>C	p.Ala288Pro	missense	Exon 6 of 7	NP_066984.1	P57789-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNK10	ENST00000319231.10	TSL:1 MANE Select	c.877G>C	p.Ala293Pro	missense	Exon 6 of 7	ENSP00000312811.5	P57789-3
KCNK10	ENST00000312350.9	TSL:1	c.877G>C	p.Ala293Pro	missense	Exon 6 of 7	ENSP00000310568.5	P57789-4
KCNK10	ENST00000340700.9	TSL:1	c.862G>C	p.Ala288Pro	missense	Exon 6 of 7	ENSP00000343104.5	P57789-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251396

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.062

Eigen

Benign

-0.093

Eigen_PC

Benign

0.016

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.011

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.055

PhyloP100

0.56

PrimateAI

Uncertain

0.68

PROVEAN

Benign

2.3

REVEL

Benign

0.24

Sift

Benign

0.61

Sift4G

Benign

0.33

Polyphen

0.90

Vest4

0.29

MutPred

0.53

Gain of catalytic residue at A284 (P = 5e-04)

MVP

0.76

MPC

0.94

ClinPred

0.52

GERP RS

4.6

Varity_R

0.36

gMVP

0.96

Mutation Taster

=52/48

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over