Variant chr17-21703629-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001194958.2(KCNJ18):c.843C>G(p.Phe281Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,610,442 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

KCNJ18
NM_001194958.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0120

Variant links:

Genes affected

KCNJ18 (HGNC:39080): (potassium inwardly rectifying channel subfamily J member 18) This gene encodes a member of the inwardly rectifying potassium channel family. Transcription of this locus is regulated by thyroid hormone, and the encoded protein plays a role in resting membrane potential maintenance. Mutations in this locus have been associated with thyrotoxic hypokalemic periodic paralysis. [provided by RefSeq, Jan 2013]

KCNJ18 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023442388).

BS2

High AC in GnomAd4 at 275 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ18	NM_001194958.2 linkuse as main transcript	c.843C>G	p.Phe281Leu	missense_variant	3/3	ENST00000567955.3	NP_001181887.2
KCNJ18	XM_005276919.4 linkuse as main transcript	c.1149C>G	p.Phe383Leu	missense_variant	2/2		XP_005276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ18	ENST00000567955.3 linkuse as main transcript	c.843C>G	p.Phe281Leu	missense_variant	3/3	1	NM_001194958.2	ENSP00000457807	P1

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

275

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.00156

AC:

2269

AN:

1458220

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1081

AN XY:

724706

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.00287

Gnomad4 ASJ exome

AF:

0.000958

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000642

Gnomad4 NFE exome

AF:

0.00179

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00181

AC:

275

AN:

152222

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000579

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.000474

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00143

AC:

174

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genetics Laboratory, Skane University Hospital Lund

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DEOGEN2

Uncertain

0.67

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.023

MetaSVM

Uncertain

0.043

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.8

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0060

Vest4

0.48

MutPred

0.69

Gain of disorder (P = 0.1433);

MVP

0.048

ClinPred

0.12

GERP RS

-7.5

Varity_R

0.44

gMVP

0.40

Splicing

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