Genetic Variant KCNK18:p.Arg10Gly (chr10-117197516-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181840.1(KCNK18):c.28A>G(p.Arg10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 1,613,430 control chromosomes in the GnomAD database, including 5,758 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 440 hom., cov: 32)

Exomes 𝑓: 0.080 ( 5318 hom. )

Consequence

KCNK18
NM_181840.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

KCNK18 (HGNC:19439): (potassium two pore domain channel subfamily K member 18) Potassium channels play a role in many cellular processes including maintenance of the action potential, muscle contraction, hormone secretion, osmotic regulation, and ion flow. This gene encodes a member of the superfamily of potassium channel proteins containing two pore-forming P domains and the encoded protein functions as an outward rectifying potassium channel. A mutation in this gene has been found to be associated with migraine with aura.[provided by RefSeq, Jan 2011]

KCNK18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015691817).

BP6

Variant 10-117197516-A-G is Benign according to our data. Variant chr10-117197516-A-G is described in ClinVar as [Benign]. Clinvar id is 1578252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK18	NM_181840.1 link	c.28A>G	p.Arg10Gly	missense_variant	Exon 1 of 3	ENST00000334549.1	NP_862823.1	Q7Z418

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK18	ENST00000334549.1 link	c.28A>G	p.Arg10Gly	missense_variant	Exon 1 of 3	1	NM_181840.1	ENSP00000334650.1		Q7Z418

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9650

AN:

152108

Hom.:

439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.0971

Gnomad ASJ

AF:

0.0866

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0727

Gnomad MID

AF:

0.0673

Gnomad NFE

AF:

0.0715

Gnomad OTH

AF:

0.0631

GnomAD3 exomes

AF:

0.0924

AC:

23199

AN:

251152

Hom.:

1340

AF XY:

0.0912

AC XY:

12382

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0931

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.0820

Gnomad NFE exome

AF:

0.0701

Gnomad OTH exome

AF:

0.0801

GnomAD4 exome

AF:

0.0800

AC:

116910

AN:

1461202

Hom.:

5318

Cov.:

AF XY:

0.0808

AC XY:

58741

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.0887

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0821

Gnomad4 NFE exome

AF:

0.0733

Gnomad4 OTH exome

AF:

0.0824

GnomAD4 genome

AF:

0.0634

AC:

9645

AN:

152228

Hom.:

440

Cov.:

AF XY:

0.0647

AC XY:

4815

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.0968

Gnomad4 ASJ

AF:

0.0866

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0727

Gnomad4 NFE

AF:

0.0715

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0677

Hom.:

212

Bravo

AF:

0.0650

TwinsUK

AF:

0.0698

AC:

259

ALSPAC

AF:

0.0739

AC:

285

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.0737

AC:

634

ExAC

AF:

0.0873

AC:

10602

Asia WGS

AF:

0.117

AC:

408

AN:

3478

EpiCase

AF:

0.0728

EpiControl

AF:

0.0718

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.44

DANN

Benign

0.55

DEOGEN2

Benign

0.15

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

REVEL

Benign

0.0030

Sift

Benign

0.26

Sift4G

Benign

0.16

Polyphen

0.028

Vest4

0.044

MPC

0.048

ClinPred

0.0018

GERP RS

-5.4

Varity_R

0.044

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over